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Molecular biology of angiotensin receptors and their role in human cardiovascular disease

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Abstract

The actions of angiotensin II in the cardiovascular system are transmitted by two known and possibly some unknown angiotensin receptor types. AT1 and AT2 both correspond to G-protein-coupled receptors with seven hydrophobic transmembrane domains, several N-glycosylation sites and a potential G-protein binding site. Cloning of coding regions and promoter sequences contributed to the understanding of receptor protein function and regulation. Angiotensin receptors with atypical binding properties for the known AT1- and AT2-specific ligands are expressed on human cardiac fibroblasts and in the human uterus. In several animal models, receptors with high affinity for angiotensin (1–7) have been described. AT1 stimulation is mediated by the generation of phospholipid-derived second messengers, activation of protein kinase C, the MAPkinase pathway and of immediate early genes. Recently, phosphorylation and dephosphorylation of tyrosine kinases have been associated with AT1- and AT2-mediated signal transduction. ATR are regulated by phosphorylation, internalization, modification of transcription rate and mRNA stability. Regulation is highly cell and organ specific and includes upregulation of ATR in some pathophysiological situations where the renin angiotensin system is activated. Whereas the function of AT1 in the cardiovascular system is relatively well established, there is little information regarding the role of AT2. Recent hypotheses suggest an antagonism between AT1 and AT2 at the signal transduction and the functional level. Transgenic animal models, particularly with targeted disruption of the AT1 and AT2 genes, suggest the contribution of both genes to blood pressure regulation. Genetic polymorphisms have been described in the AT1 and AT2 gene or neighbored regions and are used to analyze the association between gene defects and cardiovascular diseases. AT1 antagonists are now being introduced into the treatment of hypertension and potentially heart failure, and more interesting pharmacological developments are expected from the ongoing basic studies.

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Abbreviations

ACE :

Angiotensin-converting enzyme

ATR :

Angiotensin receptor

AT 1 :

Type 1 angiotensin receptor

AT 2 :

Type 2 angiotensin receptor

IP 2 :

Inositol-4,5-bis-phosphate

IP 3 :

Inositol-1,4,5-trisphosphate

IRF :

Interferon regulatory factor

References

  1. Timmermanns PBWM, Wong PC, Chiu AT et al. (1993) Angiotensin II receptors and angiotensin II receptor antagonists. Pharmacol Rev 45:205–251

    Google Scholar 

  2. Takayanagi R, Ohnaka K, Sakai Y et al. (1992) Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor. Biochem Biophys Res Commun 183:910–915

    Google Scholar 

  3. Bergsma DJ, Ellis C, Kumar C et al. (1992) Cloning and characterization of a human angiotensin II type 1 receptor. Biochem Biophys Res Commun 183:989–995

    Google Scholar 

  4. Tsuzuki S, Ichiki T, Nakakubo H et al. (1994) Molecular cloning and expression of the gene encoding human angiotensin II type 2 receptor. Biochem Biophys Res Commun 200:1449–1454

    Google Scholar 

  5. Koike G, Horiuchi M, Yamada T, Szpirer C, Jacob HJ, Dzau VJ (1994) Human type 2 angiotensin II receptor gene: cloned, mapped to the X chromosome and its mRNA is expressed in the human lung. Biochem Biophys Res Commun 203:1842–1850

    Google Scholar 

  6. Furuta H, Guo DF, Inagami T (1992) Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor. Biochem Biophys Res Commun 183:8–13

    Google Scholar 

  7. Lazard D, Briend-Sutrem MM, Villageois P, Mattei MG, Strosberg AD, Nahmias C (1994) Molecular characterization and chromosome localization of a human angiotensin II AT2 receptor gene highly expressed in fetal tissues. Receptors and Channels 2:271–280

    Google Scholar 

  8. Martin MM, Elton TS (1995) The sequence and genomic organization of the human type2 angiotensin II receptor. Biochem Biophys Res Commun 209:554–562

    Google Scholar 

  9. Regitz-Zagrosek V, Neuß M, Warnecke C, Holzmeister J, Fleck E (1995) Subtype 2 and atypical angiotensin receptors in the human heart. Basic Research Cardiol (in press)

  10. Marrero MB, Schieffer B, Paxton WG et al. (1995) Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor. Nature 375:247–250

    Google Scholar 

  11. Bumpus FM, Catt KJ, Chiu AT et al. (1991) Nomenclature for angiotensin receptors. Hypertension 17:720–723

    Google Scholar 

  12. Murphy TJ, Alexander RW, Griendling KK, Runge MS, Bernstein KE (1991) Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor. Nature 351:233–236

    Google Scholar 

  13. Sasaki K, Yarmano Y, Bardhan S et al. (1991) Cloning and expression of a complementary DNA encoding a bovine adrenal angiotensin II type-1 receptor. Nature 351:230–232

    Google Scholar 

  14. Hjorth SV, Schambye HT, Greenlee WJ, Schwartz TW (1994) Identification of peptide binding redidues in the extracellular domains of the AT1 Receptor. J Biol Chem 269:30953–30959

    Google Scholar 

  15. Wang C, Jayadev S, Escobedo JA (1995) Identification of a domain in the angiotensin II type 1 receptor determining Gq coupling by the use of receptor chimerals. JBC 270:16677–16682

    Google Scholar 

  16. Ohyama K, Yamano Y, Chaki S, Kondo T, Inagami T (1992) Domains for G-protein coupling in angiotensin II receptor type 1 studies by site-directed mutagenesis. Biochem Biophys Res Commun 189:677–683

    Google Scholar 

  17. Shirai H, Takahashi K, Katada T, Inagami T (1995) Mapping of G protein coupling sites of the angiotensin II type 1 receptor. Hypertension 25 [part 2]:726–730

    Google Scholar 

  18. Hunyady L, Bor M, Balla T, Catt KJ (1995) Critical role of a conserved intramembrane tyrosine residue in angiotensin II receptor activation. J Biol Chem 270:9702–9705

    Google Scholar 

  19. Hunyady L, Baukal AJ, Balla T, Catt CJ (1994) Independence of type I angiotensin II receptor endocytosis from G protein coupling and signal transduction. J Biol Chem 269:31378–32382

    Google Scholar 

  20. Thomas WG, Thekkakumkara TJ, Motel TJ, Baker KM (1995) Stable expression of a truncated AT1 a receptor in CHO-K1 cells. J Biol Chem 270:207–213

    Google Scholar 

  21. Kai H, Griendling KK, Lassegue B, Ollerenshaw JD, Runge MS, Alexander W (1994) Agonist-induced phosphorylation of the vascular type 1 angiotensin II receptor. Hypertension 24:523–527

    Google Scholar 

  22. Murphy TJ, Takeuchi K, Alexander RW (1992) Molecular cloning of AT1 angiotensin receptors. Am J Hypertens 5:236–242

    Google Scholar 

  23. Sandberg K, Ji H, Clark AJ, Shapira H, Catt HJ (1992) Cloning and expression of a novel angiotensin II receptor subtype. J Biol Chem 267:9455–9458

    Google Scholar 

  24. Kakar SS, Sellers JC, Devor DC, Musgrove LC, Neill JD (1992) Angiotensin II type-1 receptor subtype cDNAs: differential tissue expression and hormonal regulation. Biochem Biophys Res Commun 183:1090–1096

    Google Scholar 

  25. Iwai N, Inagami T (1992) Identification of two subtypes in the rat type I angiotensin II receptor. FEBS Lett 298:257–260

    Google Scholar 

  26. Mukoyama M, Nakajima M, Horiuchi M, Sasamura H, Pratt RE, Dzau VJ (1993) Expression cloning of type 2 angiotensin II receptor reveals a unique class of seven-transmembrane receptors. J Biol Chem 268:24539–24542

    Google Scholar 

  27. Kambayashi Y, Bardhan S, Takahashi K et al. (1993) Molecular cloning of a novel angiotensin II receptor isoform involved in phosphotyrosine phosphatase inhibition. J Biol Chem 268:24543–24546

    Google Scholar 

  28. Purcell AG, Hodges JC, Sen I, Bumpus FM, Husain A (1991) Biochemical properties of the ovarian granulosa cell type-2 angiotensin II receptors. Endocrinology 128:1947–1959

    Google Scholar 

  29. Webb ML, Lieu ECK, Cohen RB (1992) Molecular characterization of angiotensin II type II receptor in rat pheochromocytoma cells. Peptides 13:499–508

    Google Scholar 

  30. Leung KH, Roscoe WA, Smith RD, Timmermans PBMWM, Chiu AT (1992) Characterization of biochemical responses of angiotensin II (AT2) binding site in the rat pheochromocytoma PC12w cells. Eur J Pharmacol 227:63–70

    Google Scholar 

  31. Bottari SP, Taylor V, King IN (1991) Angiotensin II AT2 receptors do not interact with guanine nucleotide binding proteins. Eur J Pharmacol 207:157–163

    Google Scholar 

  32. Regitz-Zagrosek V, Friedel N, Heymann A et al. (1995) Regulation, chamber localization, and subtype distribution of angiotensin II receptors in human hearts. Circulation 91:1461–1471

    Google Scholar 

  33. Tsutsumi K, Saavedra JM (1992) Heterogeneity of angiotensin II AT-2 receptors in the rat brain. Mol Pharmacol 41:290–297

    Google Scholar 

  34. DeGasparo M, Husain A, Alexander W et al. (1995) Proposed update of angiotensin receptor nomenclature. Hypertension 25:924–927

    Google Scholar 

  35. Swanson GN, Hanesworth JM, Sardinia MF et al. (1992) Discovery of a distinct binding site for angiotensin II (3–8), a putative angiotensin IV receptor. Regul Pept 40:409–419

    Google Scholar 

  36. Harding JW, Wright JW, Swanson GN, Hanesworth JM, Krebs LT (1994) AT4 receptors: specifity and distribution. Kidney Int 46:1510–1512

    Google Scholar 

  37. Hanesworth JM, Sardinia MF, Krebs LT, Hall KL, Harding JW (1993) Elucidation of a specific binding site for angiotensin II (3–8), angiotensin IV, in mammalian heart membranes. J Pharmacol Exp. Therapeut 266:1036–1042

    Google Scholar 

  38. Harding JW, Cook VI, Miller-Wing AV et al. (1992) Identification of an AII (3–8) [AIV] binding site in guinea pig hippocampus. Brain Res 583:340–343

    Google Scholar 

  39. Kerins DM, Hao Q, Vaughan DE (1995) Angiotensin induction of PAI-1 expression in endothelial cells is mediated by the hexapeptide angiotensin IV. J Clin Invest 96:2515–2520

    Google Scholar 

  40. Wang L, Eberhard M, Erne P (1995) Stimulation of DNA and RNA synthesis of cultured rabbit cardiac fibroblasts by angiotensin IV. Eur Heart J 16 [Suppl]:451 (abstract)

    Google Scholar 

  41. Nossaman BD, Feng CJ, Kaye AD, Kadowitz PJ (1995) Analysis of responses to Ang IV: effects of PD-123319 and DuP-753 in the pulmonary circulation in the rat. Am J Physiol 268:L302-L308

    Google Scholar 

  42. Osei SY, Ahima RS, Minkes RK, Weaver JP, Khosla MC, Kadowitz PJ (1993) Differential responses to angiotensin(1–7) in the feline mesenteric and hindquaters vascular beds. Eur J Pharmacol 234:35–42

    Google Scholar 

  43. Gironacci MM, Adler-Graschinsky E, Pena C, Enero MA (1994) Effects of angiotensin II and angiotensin-(1–7) on the release of [3H]norepinephrine from rat atria. Hypertension 24:457–460

    Google Scholar 

  44. Felix D, Khosla MC, Barnes KL, Imboden H, Montani B, Ferrario CM (1991) Neurophysiological responses to angiotensin-(1–7) Hypertension 17:720–722

    Google Scholar 

  45. Mahon JM, Carr RD, Nicol AK, Henderson IW (1994) Angiotensin (1–7) is an antagonist at the type 1 angiotensin II receptor. Am J Hypertens 12:1377–1381

    Google Scholar 

  46. Pörsti I, Bara AT, Busse R, Hecker M (1994) Release of nitric oxide by angiotensin-(1–7) from porcine coronary endothelium: implications for a novel angiotensin receptor. Br J Pharmacol 111:652–654

    Google Scholar 

  47. Chaki S, Inagami T (1992) A newly found angiotensin II receptor subtype mediates cyclic GMP formation in differentiated neuro-2a cells. Eur J Pharmacol 225:355–356

    Google Scholar 

  48. Chaki S, Inagami T (1992) Identification and characterization of a new binding site for angiotensin II in mouse neuroblastoma neuro-2A cells. Biochem Biophys Res Commun 182:388–394

    Google Scholar 

  49. Sugiura GN, Hagiwara H, Hanesworth H, Hirose S (1992) Molecular cloning of porcine soluble angiotensin-binding protein. J Biol Chem 267:18067–18072

    Google Scholar 

  50. McKie N, Dando PM, Rawlings ND, Barrett AJ (1993) Thimet oligopeptidase: similarity to soluble angiotensin II-binding protein and some corrections to the published amino acid sequence of the rat testis enzyme. J Biochem 295:57–60

    Google Scholar 

  51. Eggena P, Zhu JH, Clegg K, Barrett JD (1993) Nuclear angiotensin receptors induce transcription of renin and angiotensin mRNA. Hypertens 22:496–501

    Google Scholar 

  52. Ruiz-Opazo N, Akimoto K, Herrera VLM (1995) Identification of a novel dual angiotensin II/vasopressin receptor on the basis of molecular recognition theory. Nature Med 1:1074–1081

    Google Scholar 

  53. Neuß M, Regitz-Zagrosek V, Fleck E (1994) Human cardiac fibroblasts express an angiotensin receptor with unusual binding characteristics. Biochem Biophys Res Commun 204:1334–1339

    Google Scholar 

  54. Ahmed A, Li XF, Shams M et al. (1995) Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site. J Clin Invest 96:848–857

    Google Scholar 

  55. Glossman H, Baukal A, Catt CJ (1974) Cation dependence of high affinity angiotensin II binding to adrenal cortex receptors. Science 185:281–283

    Google Scholar 

  56. Regoli D, Park WK, Rioux F (1974) Pharmacology of angiotensin. Pharmacol Rev 25:69–123

    Google Scholar 

  57. Griendling KK, Tsuda T, Berk BC, Alexander RW (1989) Angiotensin II stimulation of vascular smooth muscle cells. Secondary signalling mechanisms. Am J Hypertens 2:659–665

    Google Scholar 

  58. Sadoshima JI, Izumo S (1993) Signal transduction pathways of angiotensin II-induced c-fos gene expression in cardiac myocytes in vitro. Circ Res 73:424–438

    Google Scholar 

  59. Lokuta AJ, Cooper C, Gaa ST, Wang HE, Rogers TB (1994) Angiotensin II stimulates the release of phospholipid-derived scond messengers through multiple receptor subtypes in heart cells. J Biol Chem 269:4832–4838

    Google Scholar 

  60. Catt KJ, Balla T, Baukal AJ, Hausdorff WP, Aguilera G (1988) Control of glomerulosa cell function by angiotensin II: transduction by G-proteins and inositol phosphates. Clin Exp Pharmacol Physiol 15:501–515

    Google Scholar 

  61. Pfeilschifter J (1989) Cross-talk between transmembrane signalling systems: a prerequisite for the delicate regulation of glomerular haemodynamics by mesangial cells. Eur J Clin Invest 19:347–361

    Google Scholar 

  62. Tsuda T, Kawahara Y, Ishida Y, Koide M, Shii K, Yokoyama M (1992) Angiotensin II stimulates two myelin basic protein/microtubule-associated protein 2 kinases in cultured vascular smooth muscle cells. Circ Res 71:620–630

    Google Scholar 

  63. Oudinet JP, Russo-Marie F, Cavadore JC, Rothhut B (1993) Protein kinase C-dependent phosphorylation of annexins I and II in mesangial cells. J Biochem 292:63–68

    Google Scholar 

  64. Force T, Kyriakis JM, Avruch J, Bonvetre JV (1991) Endothelin, vasopressin and angiotensin II enhance thyrosine phosphorylation by protein kinase C-dependent pathways in glomerular messangial cells. J Biol Chem 266:6650–6656

    Google Scholar 

  65. Sadoshima J, Qui Z, Morgan JP, Izumo S (1995) Angiotensin II and other hypertrophie stimuli mediated by G-protein-coupled receptors activate thyrosine kinase, mitogen-activated protein-kinase, and 90-kD s6 kinase in cardiac myocytes. Circ Res 76:1–15

    Google Scholar 

  66. Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM (1993) Angiotensin II its mitogenic in neonatal rat cardiac fibroblasts. Circ Res 72:1245–1254

    Google Scholar 

  67. Villarreal FJ, Kim NN, Ungab GD, Printz MP, Dillmann WH (1993) Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation 88:2849–2861

    Google Scholar 

  68. Freemann EJ, Tallant EA (1994) Vascular smooth muscle cells cells contain AT1 angiotensin receptors coupled to phospholipase D activation. J Biochem 304:543–548

    Google Scholar 

  69. Bhath GJ, Thekkumkara TJ, Thomas WG, Conrad KM, Baker KM (1994) Angiotensin II stimulates sis-inducing factor-like DNA binding activity. J Biol Chem 269:31443–31449

    Google Scholar 

  70. Darnell JE, Kerr IM, Stark GR (1994) Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 264:1415–1421

    Google Scholar 

  71. Schelling JR, Singh H, Marzec R, Linas SL (1994) Angiotensin II-dependent proximal tubule sodium transport is mediated by cAMP modulation of phospholipase C. Am J Physiol 267:C1239-C1245

    Google Scholar 

  72. Johnson MC, Aguilera G (1991) Angiotensin-II receptor subtypes and coupling to signaling systems in cultured fetal fibroblasts. Endocrinol 129:1266–1274

    Google Scholar 

  73. Rossier MF, Aptel HBC, Python CP, Burnay MM, Valloton MB, Capponi AM (1995) Inhibition of low threshold caclium channels by angiotensin II in adrenal glomerulosa cells through activation of protein kinase C. J Biol Chem 270:15137–15142

    Google Scholar 

  74. Hunyady L, Rohacs T, Bago A, Deak F, Spät A (1994) Dihydropyridine-sensitive initial component of the Ang II-induced Ca2-response in adrenal glomerulosa cells. Am J Physiol 266:659–665

    Google Scholar 

  75. Bottari SP, deGasparo M, Steckelings UM, Levens NR (1993) Angiotensin II receptor subtypes: characteriziation, signalling mechanisms, and possible physiological implications. Front Neuroendocrinol 14:123–171

    Google Scholar 

  76. Buisson B, Laflamme L, Bottari SP, DeGasparo M, Gallo-Payett N, Payet M (1995) A G-protein is involved in the angiotensin AT2 receptor inhibition of the T-type calcium current in non-differentiated NG108–15 cells. J Biol Chem 270:1670–1674

    Google Scholar 

  77. Nahmias S, Cazaubon SM, Briend-Sutren MM, Lazard D, Villageois P, Strosberg AD (1995) Angiotensin AT 2 receptors are functionally coupled to protein tyrosine dephosporylation in NIE-115 neuroblastoma cells. J Biochem 306:87–92

    Google Scholar 

  78. Nakajima M, Huchtinson HG, Fujinaga M et al. (1995) The angiotensin II type 2 (AT2) receptor antagonizes the growth effects of the AT1 receptor: gain-of-function study using gene transfer. Proc Natl Acad Sci USA 92:10663–10667

    Google Scholar 

  79. Stoll M, Steckelings UM, Paul M, Bottari SP, Metzger R, Unger T (1995) The angiotensin AT2-receptor mediates inhibition of cell proliferation in coronary endothelial cells. J Clin Invest 95:651–657

    Google Scholar 

  80. Kang J, Posner P, Sumners C (1994) Angiotensin II type 2 receptor stimulation of neuronal K+ currensts involves an inhibitory GTP binding protein. Am J Physiol 267:C1389-C1397

    Google Scholar 

  81. Iwai N, Yamano Y Chaki S et al. (1991) Rat angiotensin II receptor cDNA sequence and regulations of the gene expression. Biochem Biophys Res Commun 177:299–304

    Google Scholar 

  82. Elton TS, Stephan CC, Taylor GR et al. (1992) Isolation of two distinct type I angiotensin II receptor genes. Biochem Biophys. Res Commun 184:1067–1073

    Google Scholar 

  83. Yoshida H, Kakuchi J Guo DP, Furuta H, Iwai N (1992) Analysis of the evolution of angiotensin II type 1 receptor gene in mammals (mouse, rat, bovine and human) Biochem Biophys Res Commun 186:1042–1049

    Google Scholar 

  84. Aiyar N, Baker E, Wu HL et al. (1994) Human AT1 receptor is a single copy gene: characterization in a stable cell line. Mol Cell Biochem 131:75–86

    Google Scholar 

  85. Su B, Martin MM, Beason KB, Miller PJ, Elton TS (1994) The genomic organization and functional analysis of the promoter for the human angiotensin II type 1 receptor. Biochem Biophys Res Commun 204:1039–1046

    Google Scholar 

  86. Guo D, Furuta H, Mizukoshi M, Inagami T (1994) The genomic organisation of human angiotensin II type 1 receptor. Biochem Biophys Res Commun 200:313–319

    Google Scholar 

  87. Curnow KM, Pascoe L, White PC (1992) Genetic analysis of the human type-1 angiotensin II receptor. Mol Endocrinol 6:1113–1118

    Google Scholar 

  88. Chassagne C, Beatty BG, Meloche S (1995) Assignment of the human angiotensin II type 2 receptor gene (AGTR2) to chromosome Xq22-q23 by fluorescence in situ hybridization. Genomics 25:601–693

    Google Scholar 

  89. Warnecke C, Holzmeister J, Regitz-Zagrosek V, Fleck E (1995) Nucleotide sequence of the 5′-untranslated region of the angiotensin II receptor subtype 2 messenger obtained by one-side-specific polymerase chain reaction as precondition for the identification of the promoter. Eur Heart J 16 [Suppl]:365 (abstract)

    Google Scholar 

  90. Ichiki T, Inagami T (1995) Transcriptional regulation of the mouse angiotensin II type 2 receptor gene. Hypertension 25:720–725

    Google Scholar 

  91. Ullian ME, Linas SL (1989) Role of receptor cycling in the regulation of angiotensin II surface receptor number and angiotensin II uptake in rat vascular smooth muscle cells. J Clin Invest 84:840–846

    Google Scholar 

  92. Bouvier M, Collins S, O'Dowd BF et al. (1989) Two distinct pathways for cAMP-mediated down-regulation of the β2-adrenergic receptor. J Biol Chem 264:16786–16792

    Google Scholar 

  93. Collins S, Bouvier M, Bolanowski MA, Caron MG, Lefkowitz RJ (1989) cAMP stimulates transcription of the β2-adrenergic receptor gene in response to short-term agonist exposure. Biochemistry 86:4853–4857

    Google Scholar 

  94. Hausdorff WP, Caron MG, Lefkowitz RJ (1990) Turning off the signal: desensitization of β-adrenergic receptor function. FASEB 4:2881–2889

    Google Scholar 

  95. Lohse MJ, Benovic JL, Caron MG, Lefkowitz RJ (1990) Multiple pathways of rapid β2-adrenergic receptor desensitization. J Biol Chem 265:3202–3209

    Google Scholar 

  96. Lefkowitz RJ, Inglese J, Koch WJ, Pitcher J, Attramadal H, Caron MG (1990) Role of phosphorylation in desentizitation of the β-adrenoreceptor. Trends Pharmacol Sci 11:190–194

    Google Scholar 

  97. Sibley DR, Lefkowitz RJ (1985) Molecular mechanisms of receptor desensitization: delineation with specific inhibitors. Nature 317:124–129

    Google Scholar 

  98. Hausdorff WP, Bouvier M, O'Dowd BF, Irons GP, Caron MG, Lefkowitz RJ (1989) Phosphorylation sites on two domains of the β2 adrenergic receptor are involved in distinct pathways of receptor desensitization. JBC 264:12657–12665

    Google Scholar 

  99. Hein L, Sasamura H, Pratt RE, Dzau VJ, Kobilka BK (1993) Cellular trafficking of angiotensin II and its AT-1 receptor. Circulation 88 [Suppl I]:281(abstract)

    Google Scholar 

  100. Brock TA, Rittenhouse SE, Powers CW, Ekstein LS, Gimbrone MA, Alexander RW (1985) Phorbol ester and 1-oleoyl-2-acetylglycerol inhibit angiotensin activation of phospholipase C in cultured vascular smooth muscle cells. J Biol Chem 260:14158–14162

    Google Scholar 

  101. Abdellatif MM, Neubauer FC, Lederer WJ, Rogers TB (1991) Angiotensin-induced desensitization of the phosphoinositide pathway in cardiac cells occurs at the level of the receptor. Circ Res 69:800–809

    Google Scholar 

  102. Tang H, Shirai H, Inagami T (1995) Inhibition of protein kinase C prevents rapid desensitization of type 1 B angiotensin II receptor. Circ Res 77:239–248

    Google Scholar 

  103. Nickenig G, Murphy TJ (1994) Down-regulation by growth factors of vascular smooth muscle angiotensin receptor gene expression. Mol Pharmacol 46:653–659

    Google Scholar 

  104. Murphy TJ, Nickenig G (1995) Enhanced mRNA degradation in vascular smooth muscle cells: a mechanism for heterologous down-regulation of AT1, 5HT2 and thrombin receptors. FASEB 9:271(abstract)

    Google Scholar 

  105. Murasawa S, Matsubara H, Urakami M, Inada M (1993) Regulatory elements that mediate expression of the gene for the angiotensin II type 1 a receptor for the rat. J Biol Chem 268:26996–27003

    Google Scholar 

  106. Uno S, Guo DF, Nakajama M et al. (1994) Glucocorticoid induction of rat angiotensin II type 1A receptor gene promoter. Biochem Biophys Res Commun 204:210–215

    Google Scholar 

  107. Murasawa S, Matsubara H, Kanasaki M et al. (1995) Characterization of glucocorticoid response element of rat angiotensin II type 1A receptor gene. Biochem Biophys Res Commun 209:832–840

    Google Scholar 

  108. Guo DF, Uno S, Ishihata A, Nakamura N, Inagami T (1995) Identification of a cis-acting glucocorticoid responsive element in the rat angiotensin II type 1A promoter. Circ Res 77:249–257

    Google Scholar 

  109. Guo DF, Inagami T (1994) Epidermal growth factor-enhanced human angiotensin II type 1 receptor. Hypertension 23:1032–1035

    Google Scholar 

  110. Su B, Elton TS (1994) Molecular structure and transcriptional function of the human type-1A angiotensin II receptor gene. Circulation 90:1342

    Google Scholar 

  111. Lu D, Sumners C, Raizada MK (1994) Regulation of angiotensin II type 1 receptor mRNA in neuronal cultures of normotensive and spontaneously hypertensive rat brains by phorbol esters and forskolin. J Neurochem 62:2079–2084

    Google Scholar 

  112. Holzmeister J, Warnecke C, Regitz-Zagrosek V, Fleck E (1995) The angiotensin II type 1 receptorgene promoter is inducible with phorbol-ester but not with forskolin. Eur Heart J 16 [Suppl]:364 (abstract)

    Google Scholar 

  113. Horiuchi M, Koike G, Yamada T, Mukoyama M, Nakajima M, Dzau VJ (1995) The growth-dependent expression of angiotensin II type 2 receptor is regulated by transcription factors interferon regulatory factor-1 and -2. J Biol Chem 270:20225–20230

    Google Scholar 

  114. Ichiki T, Inagami T (1995) Expression, genomic organization, and transcription of the mouse angiotensin II type 2 receptor gene. Circ Res 76:693–700

    Google Scholar 

  115. Matsubara H, Kanasaki M, Murasawa S, Tsukaguchi Y, Nio Y, Inada M (1994) Differential gene expression and regulation of angiotensin II receptor subtypes in rat cardiac fibroblasts and cardiomyocytes in culture. J Clin Invest 93:1592–1601

    Google Scholar 

  116. Ullian ME, Schelling RJ, Linas SL (1992) Aldosterone enhances angiotensin II receptor binding and inositol phosphate responses. Hypertension 20:67–73

    Google Scholar 

  117. Makita N, Iwai N, Inagami T, Badr KF (1992) Two distinct pathways in the down-regulation of type-1 angiotensin II receptor gene in rat glomerular mesangial cells. Biochem Biophys Res Commun 185:142–146

    Google Scholar 

  118. Myers LM, Sumners C (1989) Regulation of angiotensin II binding sites in neuronal cultures by catecholamines. Am J Physiol 257:706–713

    Google Scholar 

  119. Williams B, Tsai P, Schrier RW (1992) Glucose-induced downregulation of angiotensin II and arginine vasopressin receptors in cultured rat aortic vascular smooth muscle cells. Role of protein kinase C. J Clin Invest 90:1992–1995

    Google Scholar 

  120. Kalinyak JE, Sechi LA, Griffin CA et al. (1993) The renin-angiotensin system in streptozotocin-induced diabetes mellitus in the rat. J Am Soc Nephrol 4:1337–1345

    Google Scholar 

  121. Dudley DT, Summerfelt RM (1993) Regulated expression of angiotensin II (AT2) binding sites in R3T3 cells. Peptides 44:199–206

    Google Scholar 

  122. Ichiki T, Kambayashi Y, Inagami T (1995) Multiple growth factors modulate mRNA expression of angiotensin II type-2 receptor in R3T3 cells. Circ Res 77:1070–1076

    Google Scholar 

  123. Hu ZW, Shi XY, Okazaki M, Hoffman BB (1995) Angiotensin II induces transcription and expression of alpha-1-adrenergic receptors in vascular smooth muscle cells. Am J Physiol 268:H1006-H1014

    Google Scholar 

  124. Regitz-Zagrosek V, Auch-Schwelk W, Neuß M, Fleck E (1994) Regulation of the ATR subtypes in cell cultures, animal models and human diseases. Eur Heart J 15 [Suppl D]:92–97

    Google Scholar 

  125. Iwai N, Inagami T (1992) Regulation of the expression of the rat angiotensin II receptor mRNA. Biochem Biophys Res Commun 182:1094–1099

    Google Scholar 

  126. Llorens-Cortes C, Greenberg B, Huang H, Corvol P (1994) Tissular expression and regulation of type 1 angiotensin II receptor subtypes by quantitative reverse transcriptase-polymerase chain reaction analysis. Hypertension 24:538–548

    Google Scholar 

  127. Du Y, Yao A, Guo D, Inagami T, Wang DH (1995) Differential regulation of angiotensin II receptor subtypes in rat kidney by low dietary sodium. Hypertension 25:872–877

    CAS  PubMed  Google Scholar 

  128. Kitami Y, Okura T, Marumoto K, Wakamiya R, Hiwada K (1992) Differential gene expression and regulation of type-1 angiotensin II receptor subtypes in the rat. Biochem Biophys Res Commun 188:446–452

    Google Scholar 

  129. Haefliger J-A, Bergonzelli G, Waeber G et al. (1995) Renin and angiotensin II receptor gene expression in kidneys of renal hypertensive rats. Hypertension 26:733–737

    Google Scholar 

  130. Suzuki J, Matsubara H, Urakami M, Inada M (1993) Rat angiotensin II (type 1A) receptor mRNA regulation and subtype expression in myocardial growth and hypertrophy. Circ Res 73:439–447

    Google Scholar 

  131. Iwai N, Inagami T, Ohmichi N, Nakamura Y, Saeki Y, Kinoshita M (1992) Differential regulation of rat AT1a and AT1b receptor mRNA. Biochem Biophys Res Commun 188:298–303

    Google Scholar 

  132. Fuji N, Tanaka M, Ohnishi J et al. (1995) Alterations of angiotensin receptor contents in hypertrophied hearts. Biochem Biophys Res Commun 212:326–333

    Google Scholar 

  133. Lambert C, Massillon Y, Meloche S (1995) Upregulation of cardiac angiotensin II AT1 receptors in congenital cardiomyopathic hamsters. Circ Res 1001–1007:77

    Google Scholar 

  134. Sadoshima JI, Izumo S (1993) Molecular characterization of angiotensin II-induced hypertrophy of cardiac myocytes and hyperplasia of cardiac fibroblasts. Circ Res 73:413–423

    Google Scholar 

  135. Sernia C, Marchant C, Brown L, Hoey A (1993) Cardiac angiotensin receptors in experimental hyperthyroidism in dogs. Cardiovasc Res 27:423–428

    Google Scholar 

  136. Regitz-Zagrosek V, Auch-Schwelk W, Hess B et al. (1995) Tissue and subtype specific modulation of angiotensin II receptors by chronic treatment with cyclosporin A, ACE-inhibitors and AT1 antagonists. J Cardiovasc Pharmacol 26:66–72

    Google Scholar 

  137. Auch-Schwelk W, Bossaller C, Götze S, Thelen J, Fleck E (1993) Endothelial and vascular smooth muscle function after chronic treatment with cyclosporin A. J Cardiovasc Pharmacol 21:435–440

    Google Scholar 

  138. Auch-Schwelk W, Duske E, Hink U, Betz M, Unkelbach M, Fleck E (1994) Vasomotor responses in cyclosporin A-treated rats after chronic angiotensin blockade. Hypertension 23:832–837

    Google Scholar 

  139. Baxter CR, Duggin GG, Willis NS, Hall BM, Tiller DJ (1982) Cyclosporin A-induced increases in renin storage and release. Res Commun Chem Pathol Pharmacol 37:305–312

    Google Scholar 

  140. Meggs LG, Coupet J, Huang H et al. (1993) Regulation of angiotensin II receptors on ventricular myocytes after myocardial infarction in rats. Circ Res 72:1149–1162

    Google Scholar 

  141. Reiss K, Capasso JM, Huang HE, Meggs LG, Li P, Anversa A (1993) ANG II receptors, c-myc, and c-jun in myocytes after myocardial infarction and ventricular failure. Am J Physiol 264:760–767

    Google Scholar 

  142. Nio Y, Murasawa S, Kanasaki M, Inada M (1995) Regulation of gene transcription of ANG II receptor subtypes in myocardial infarction. J Clin Invest 95:46–54

    Google Scholar 

  143. Lopez JJ, Lorell BH, Ingelfinger JR et al. (1994) Distribution and function of cardiac angiotensin AT1 and AT2-receptor subtypes in hypertrophied rat hearts. Am J Physiol 36:H844-H852

    Google Scholar 

  144. Urata H, Boehm KD, Philip A et al. (1993) Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest 91:1269–1281

    Google Scholar 

  145. Suzuki H, Shibata H, Murakami M et al. (1995) Modulation of angiotensin II type 1 receptor mRNA expression in human blood cells: comparison of platelets and mononuclear leucocytes. J Endocrinol 42:15–22

    Google Scholar 

  146. Friedrich SP, Lorell BH, Rousseau MF et al. (1994) Intracardiac angiotensin-converting enzyme inhibition improves diastolic function in patients with left ventricular hypertrophy due to aortic stenosis. Circulation 90:2761–2771

    Google Scholar 

  147. Foult JM, Tavolaro O, Antony I, Nitenberg A (1989) Coronary vasodilation induced by intracoronary enalaprilat: an argument for the role of the local renin-angiotensin system in patients with dilated cardiomyopathy. Eur J Heart 10 [Suppl F]:97–100

    Google Scholar 

  148. Haber HL, Powers ER, Gimple LW et al. (1994) Intracoronary angiotensin-convering enzyme inhibition improves diastolic function in patients with hypertensive left ventricular hypertrophy. Circulation 89:2616–2625

    Google Scholar 

  149. Nozawa YHA Oda N, et al. (1994) Angiotensin II receptor subtypes in bovine and human ventricular myocardium. J Pharmacol Exp Ther 270:566–571

    Google Scholar 

  150. Lindpaintner K, Ganten D (1991) The cardiac renin angiotensin system: an appraisal of present clinical and experimental evidence. Circ Res 69:475–482

    Google Scholar 

  151. Linz W, Schölkens B, Lindpaintner K, Ganten D (1989) Cardiac-renin-angiotensin system. Am J Hypertens 2:301–310

    Google Scholar 

  152. Linz WSB Lindpaintner K, Ganten D (1989) Cardiac renin angiotensin system. Am J Hypertension 2:301–310

    Google Scholar 

  153. Schelling P, Fischer H, Ganten D (1991) Angiotensin and cell growth: a link to cardiovascular hypertrophy? J Hypertens 9:3–15

    Google Scholar 

  154. Urata H, Healy B, Stewart RW, Bumpus FM, Husian A (1989) Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 69:54–66

    Google Scholar 

  155. Brink M, deGasparo M, Rogg H, Schmid A, Bullock G (1995) Localization of the angiotensin AT2 receptor subtype in the human heart. Circulation 92 [Suppl I]:1–63

    Google Scholar 

  156. Gräfe M, Auch-Schwelk W, Graf K et al. (1993) Induction of the adhesion molecule E-selectin in human cardiac endothelial cells by angiotensin II. Circulation 88:1–316

    Google Scholar 

  157. Dostal DE, Baker KM (1992) Angiotensin II stimulation of left ventricular hypertrophy in adult rat heart. Am J Hypertens 5:276–280

    Google Scholar 

  158. Dostal DE, Baker KM (1993) Evidence for a role of an intracardiac renin angiotensin system in normal and failing hearts. Trend Cardiovasc Med 3:67–74

    Google Scholar 

  159. Beinlich CJ, White GJ, Baker KM, Morgan HE (1991) Angiotensin II and left ventricular growth on newborn pig heart. J Mol Cell Cardiol 23:1031–1038

    Google Scholar 

  160. Baker KM, Aceto JF (1990) Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol 259:H610-H618

    Google Scholar 

  161. Holubarsch C, Hasenfuss G, Schmidt-Schweda S et al. (1993) Angiotensin I and II exert inotropic effects in atrial but not in ventricular human myocardium. Circulation 88:1228–1237

    Google Scholar 

  162. Sadoshima JI, Xu Y, Slayter HS (1993) Autocrine release of angiotensin II mediates stretch-induced hypertrophy of cardiac myocytes in vitro. Cell 75:977–984

    Google Scholar 

  163. Yamazaki T, KomuroI, Kudoh S et al. (1995) Angiotensin II partly mediates mechanical stress-induced cardiac hypertrophy. Circ Res 258–265

  164. Neyses L, Nouskas J, Luyken J et al. (1993) Induction of immediate-early genes by angiotensin II and endothelin-1 in adult rat cardiomyocytes. J Hypertens 11:927–934

    Google Scholar 

  165. Naftilan AJ, Pratt RE, Eldridge CS, Lin HL, Dzau VJ (1989) Angiotensin II induces c-fos expression in smooth muscle via transcriptional control. Hypertension 13:706–711

    Google Scholar 

  166. Naftilan AJ, Pratt RE, Dzau VJ (1989) Induction of platelet-derived growth factor a-chain and c-myc gene expressions by angiotensin II in cultured rat vascular smooth muscle cells. J Clin Invest 83:1419–1424

    Google Scholar 

  167. Naftilan AJ, Gilliland GK, Eldridge CS, Kraft AS (1990) Induction of the proto-oncogene c-jun by angiotensin II. Mol Cell Biol 10:5536–5540

    Google Scholar 

  168. Everett AD, Tufro-McReddie A, Fisher A, Gomez A (1994) Angiotensin receptor regulates cardiac hypertrophy and transforming growth factor-β1 expression. Hypertens 23:587–592

    Google Scholar 

  169. Baker KM, Chemin MI, Wixson SK, Aceto JF (1990) Renin-angiotensin system involvement in pressure-overload cardiac hypertrophy in rats. Am J Physiol 259:H324-H332

    Google Scholar 

  170. Crawford DC, Chobonian AV, Brecher P (1994) Angiotensin II induces fibronectin expression associated with cardiac fibrosis in the rat. Circ Res 74:727–739

    Google Scholar 

  171. Focaccio A, Volpe M, Ambrosio G et al. (1993) Angiotensin II directly stimulates release of atrial natriuretic factor in isolated rabbit hearts. Circulation 87:192–198

    Google Scholar 

  172. Stouffer GA, K. OG (1992) Angiotensin II-induced mitogenesis of spontaneously hypertensive rat-derived cultured smooth muscle cells is dependent on autocrine production of transforming growth factor-β. Circ Res 70:820–828

    Google Scholar 

  173. Turla MB, Thompson MM, Corjay MH, Owens GK (1991) Mechanisms of angiotensin II-and arginine vasopressin-induced increases in protein synthesis and content in cultured rat aortic smooth muscle cells. Circ Res 68:288–299

    Google Scholar 

  174. Holycross BJ, Peach MJ, Owens GK (1993) Angiotensin II stimulates increased protein synthesis, not increased DNA synthesis, in intact rat aortic segments, in vitro. J Vasc Res 30:80–86

    Google Scholar 

  175. Weber H, Taylor DS, Molloy CJ (1994) Angiotensin II induces delayed mitogenesis and cellular proliferation in rat aortic smooth muscle cells. J Clin Invest 93:788–798

    Google Scholar 

  176. Kauffmann RE, Bean JS, Zimmermann KM, Brown RF, Steinberg MI (1991) Losartan, a nonpeptide angiotensin II (ang II) receptor antagonist, inhibits neointima formation following ballon injury to rat carotid arteries. Life Sci 49:223–228

    Google Scholar 

  177. Viswanathan M, Strömberg C, Seltzer A, Saavedra JM (1992) Balloon angioplasty enhances the expression of angiotensin II AT1 receptors in neointima of rat aorta. J Clin Invest 90:1707–1712

    Google Scholar 

  178. Chua CC, Diglio CA, Siu BB, Chua BHL (1994) Angiotensin II induces TGF-β1 production in rat heart endothelial cells. Biochim Biophys Acta 1223:141–147

    Google Scholar 

  179. Feener EP, Northrup JM, Aiello LP, King GL (1995) Angiotensin II induces plasminogen activator-inhibitor-1 and -2 expression in vascular endothelial and smooth muscle cells. J Clin Invest 95:1353–1362

    Google Scholar 

  180. Ridker PM, Gaboury CL, Conlin PR, Seely EW, Williams GH, Vaughan DE (1993) Stimulation of plasminogen activator inhibitor in vivi by infusion of angiotensin II. Circulation 87:1969–1973

    Google Scholar 

  181. Janiak P, Pillon A, Prost JF, Vilaine JP (1992) Role of angiotensin subtype 2 receptor in neointima formation after vasculary injury. Hypertension 20:737–745

    Google Scholar 

  182. Yamada T, Horiuchi M, Dzau VJ (1995) Mitogen-activated protein (MAP) kinase dephosphorylation by angiotensin II type 2 receptor induces apoptosis. Circulation 92 [Suppl I]:499 (abstract)

    Google Scholar 

  183. Bennett MR, Evan GI, Schwartz SM (1995) Apoptosis of human vascular smooth muscle cells derived from normal vessels and coronary atherosclerotic plaques. J Clin Invest 95:2266–2274

    Google Scholar 

  184. Viswanathan M, Saavedra JM (1992) Expression of angiotensin II AT2 receptors in the rat skin during experimental wound healing. Peptides 13:783–786

    Google Scholar 

  185. Kimura B, Sumners C, Phillips MI (1992) Changes in skin angiotensin II receptors in rats during wound healing. Biochem Biophys Res Commun 187:1083–1090

    Google Scholar 

  186. Gräfe M, Zakrzewicz A, Auch-Schwelk W, Graf K, Regitz-Zagrosek V, Gaethgens P (1995) Angiotensin II induced leucocyte adhesion to human coronary endothelial cells is mediated by E-Selectin. Eur Heart J 16 [Suppl]:274 (abstract)

    Google Scholar 

  187. Scheuer D, Perrone M (1993) Angiotensin type 2 receptors mediate depressor phase of biphasic pressure response to angiotensin. Am J Physiol 264:R917–923

    Google Scholar 

  188. Ito M, Oliverio MI, Mannon PJ et al. (1995) Regulation of blood pressure by the type 1a angiotensin II receptor gene. Proc Natl Acad Sci USA 92:3521–3525

    Google Scholar 

  189. Ichiki T, Labolsky PA, Shiota C et al. (1995) Effects on blood pressure and exploratory behaviour of mice lacking angiotensin II type-2 receptor. Nature 377:748–750

    Google Scholar 

  190. Hein L, Barsh GS, Pratt RE, Dzau VJ, Kobilka BK (1995) Behavioural and cardiovascular effects of disrupting the angiotensin II type-2 receptor gene in mice. Nature 377:744–747

    Google Scholar 

  191. Tanimoto K, Sugiyama F, Goto Y et al. (1994) Angiotensinogen-deficient mice with hypotension. J Biol Chem 269:31334–31337

    Google Scholar 

  192. Smithies O, Kim H-S (1994) Targeted gene duplication and disruption for analyzing quantitative genetic traits in mice. Proc Natl Acad Sci USA 91:3612–3615

    Google Scholar 

  193. Williams GH, Dluhy RG, Lifton RP et al. (1992) Non-modulation as an intermediate phenotype in essential hypertension. Hypertension 20:788–796

    Google Scholar 

  194. Bonnardeaux A, Davies E, Jeunamaitre X et al. (1994) Angiotensin II type 1 receptor gene polymorphisms in human essential hypertension. Hypertension 24:63–69

    Google Scholar 

  195. Doria A, Warram JH, Krolewski AS (1994) Ddel polymorphism in the AGTR1 gene. Hum Mol Genet 3:1444

    Google Scholar 

  196. Rolfs A, Kallisch H, Weber I, Regitz-Zagrosek V, Fleck E (1994) A MnII polymorphism at base pair 570 of the human angiotensin II, subtype 1 receptor gene. Human molecular genetics 3:213–214

    Google Scholar 

  197. Rolfs A, Weber-Rolfs I, Regitz-Zagrosek V, Kallisch H, Riedel K, Fleck E (1994) Genetic polymorphisms of the angiotensin II type 1 (AT1) receptor gene. Eur Heart J 15 [Suppl D]:108–112

    Google Scholar 

  198. Davies E, Bonnardeaux A, Lathrup GM, Corvol P, Clauser E, Soubrier F (1994) Angiotensin II (type 1) receptor locus: CA repeat polymorphism and genetic mapping. Hum Mol Genet 3:838

    Google Scholar 

  199. Tiret L, Bonnardeaux A, Poirier O et al. (1994) Synergistic effects of angiotensin-converting enzyme and angiotensin-II type 1 receptor gene polymorphisms on risk of myocardial infarction. Lancet 344:910–913

    Google Scholar 

  200. Benetos A, Topouchian J, Ricard S et al. (1995) Influence of angiotensin II type 1 receptor polymorphism on aortic stiffness in never-treated hypertensive patients. Hypertension 26:44–47

    Google Scholar 

  201. Katsuya T, Horiuchi M, Koike G, Dzau VJ (1995) Cloning and characterization of human angiotensin II type receptor gene and its polymorphism. Circulation 92 [Suppl I]:1–282

    Google Scholar 

  202. Koike G, Horiuchi M, Winer ES, Brown DM, Dzau VJ, Jacob HJ (1995) Cloning, characterization and genetic mapping of the rat type 2 angiotensin receptor gene. Circulation 92 [Suppl I]:1–282

    Google Scholar 

  203. Smith RD, Chiu AT, Wong PC, Herblin WF, Timmermans PBMWM (1992) Pharmacology of nonpeptide angiotensin II receptor antagonists. Annu Rev Pharmacol Toxicol 32:135–165

    Google Scholar 

  204. Weber MA (1992) Clinical experience with the angiotensin II receptor antagonist losartan, a preliminary report. Am J Hypertens 5:247–251

    Google Scholar 

  205. Goldberg MR, Bradstreet TE, McWilliams EJ et al. (1995) Biochemical effects of losartan, a nonpeptide angiotensin I receptor antagonist, on the renin-angiotensin-aldosterone system in hypertensive patients. Hypertension 25:37–42

    Google Scholar 

  206. Hood S, Nicholle M, Gilebriet NL (1987) Cough with angiotensin-converting enzyme inhibitors. NZ Med J 100:6–7

    Google Scholar 

  207. Yeo WW, Ramsey EE (1990) Persistent dry cough with enalalpril: incidence depends on method used. J Human Hypertens 4:517–520

    Google Scholar 

  208. Sweet CS, Rucinska EJ (1994) Losartan in heart failure: preclinical experiences and initial clinical outcomes. Eur Heart J 15 [Suppl D]:139–144

    Google Scholar 

  209. Gottlieb SS, Dickstein K, Fleck E et al. (1993) Hemodynamic and neurohormonal effects of the angiotensin antagonist losartan in patients with congestive heart failure. Circulation 88:1602–1609

    Google Scholar 

  210. Crozier J, Ikram H, Awan N (1995) Losartan in heart failure: hemodynamic effects and tolerability. Circulation 91:691–697

    Google Scholar 

  211. Goldberg MR, Tanaka W, Barchowsky A (1993) Effects of losartan and blood pressure, plasma renin activity and angiotensin II in volunteers. Hypertension 21:704–713

    Google Scholar 

  212. Regitz-Zagrosek V, Neuss M, Holzmeister J, Fleck E (1995) Use of angiotensin II antagonists in human heart failure: function of the subtype 1 receptor. J Hypertens 13 [Suppl I]:63–71

    Google Scholar 

  213. Johnson RM, Garrison JC (1987) Epidermal growth factor and angiotensin II stimulate formation of inositol 1, 4, 5-and inositol 1, 3, 4-trisphosphate in hepatocytes. Differential inhibition by pertussis toxin and phorbol 12-myristate 13-acetate. J Biol Chem 262:17285–17293

    Google Scholar 

  214. Pfeilschifter J, Huwiler A, Merriweather C, Briner VA (1992) Angiotensin II stimulation of phospholipase D in rat renal mesangial cells is mediated by the AT1 receptor subtype. Eur J Pharmacol 225:57–62

    Google Scholar 

  215. Kapas S, Hinson JP, Puddefoot JR, Ho MM, Vinson GP (1994) Internalization of the type 1 angiotensin II receptor (AT1) is required for protein kinase C activation but not for inositol trisphosphate release in the angiotensin II stimulated rat adrenal zona glomerulosa cell. Biochem Biophys Res Commun 204:1292–1298

    Google Scholar 

  216. Booz GW, Dostal GE, Singer HA, Baker KM (1994) Ivolvement of protein kinase C and Ca2+ in angiotensin II-induced mitogenesis of cardiac fibroblasts. Am J Physiol 267:1308–1318

    Google Scholar 

  217. Marrero MB, Schieffer B, Paxton WG, Schieffer E, Bernstein KE (1995) Electroporation of pp60c-src antibodies inhibits the angiotensin II activation of phospholipase C-y1 in rat aortic smooth muscle cells

  218. Duff JL, Berk BC, Corson MA (1992) Angitensin II stimulates the pp44 and pp42 miotgen-activated protein kinases in cultured rat aortic smooth muscle cells. Biochem Biophys Res Commun 188:257–264

    Google Scholar 

  219. Itho H, Mukoyama M, Pratt RE, Gibbons GH, Dzau VJ (1993) Multiple autocrine growth factors modulate vascular smooth muscle cell growth response to angiotensin II. J Clin Invest 91:2268–2274

    Google Scholar 

  220. Rupprecht HD, Dann P, Sukhatme VP, Sterzel RB, Coleman DL (1992) Effect of vasoactive agents on the induction of Egr-1 in rat mesangial cells: correlation with mitogenicity. Am J Physiol 263:F623–636

    Google Scholar 

  221. Dubey RK, Roy A, Overbeck HW (1992) Culture of renal arteriolar smooth muscle cells. Mitogenic response to angiotensin II. Circ Res 71:1143–1152

    Google Scholar 

  222. Liu G, Espinosa E, Luscher TF (1995) Angiotensin II stimulates migration of human vascular smooth muscle cells via AT1 receptors. Eur J Clin Invest 25 [Suppl 2]

  223. Barnes JM, Barber PC, Barnes NM (1991) Identification of angiotensin II receptor subtypes in human brain. Neurorep 2:605–608

    Google Scholar 

  224. Sechi L, Grady E, Griffin CA, Kalinyak JE, Schambelan M (1992) Distribution of angiotensin II receptor subtypes in rat and human kidney. Am J Physiol 262:F236-F240

    Google Scholar 

  225. Grone HJ, Simon M, Fuchs E (1992) Autoradiographic char acterization of angiotensin receptor subtypes in fetal and adult human kidney. Am J Physiol 262:326F-331F

    Google Scholar 

  226. Naville D, Lebrethon MC, Kermabon AY, Rouer E, Benarous R, Saez JM (1993) Characterization and regulation of the angiotensiin II type-1 receptor-binding and mRNA in human adrenal fasciculata-reticularis cells. FEBS Letters 321:184–188

    Google Scholar 

  227. Whitebread S, Mele M, Kamber B, DeGasparo M (1989) Preliminary biochemical characterization of two angiotensin II receptor subtypes. Biochem Biophys Res Commun 163:284–291

    Google Scholar 

  228. Kalenga MK, DeGasparo M, Dehertogh R, Whitebread S, Van Krieken L, Thomas K (1991) Angiotensin II receptors in the human placenta are type AT1. Reprod Nutr Dev 31:257–267

    Google Scholar 

  229. Vinson GP, Puddefoot JR, Ho MM et al. (1995) Type 1 angiotensin II receptors in rat and human sperm. J Endocrinol 144:369–378

    Google Scholar 

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  1. Department of Internal Medicine/Cardiology, Virchow-Klinikum, Humboldt Universität, and Deutsches Herzzentrum Berlin, Augustenburger Platz 1, D-13353, Berlin, Germany

    V. Regitz-Zagrosek, M. Neuß, J. Holzmeister, C. Warnecke & E. Fleck

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Regitz-Zagrosek, V., Neuß, M., Holzmeister, J. et al. Molecular biology of angiotensin receptors and their role in human cardiovascular disease. J Mol Med 74, 233–251 (1996). https://doi.org/10.1007/BF00196577

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