Heart Failure Reviews

, Volume 13, Issue 3, pp 355–365 | Cite as

Hypertension, RAS, and gender: what is the role of aminopeptidases?

  • María Jesús Ramírez-Expósito
  • José Manuel Martínez-Martos


Hypertension is the major risk factor for coronary heart disease, stroke, and renal disease. Also, it is probably the most important risk factor for peripheral vascular disease and vascular dementia. Although hypertension occurs in both men and women, gender differences have been observed. However, whether sex hormones are responsible for the observed gender-associated differences in arterial blood pressure, and which is their mechanism of action, remains unclear. Local and circulating renin–angiotensin systems (RAS) are examples of systems that may be involved in the pathogenesis of hypertension. Classically, angiotensin II (Ang II) has been considered as the effector peptide of the RAS, but Ang II is not the only active peptide. Several of its degradation products, including angiotensin III (Ang III) and angiotensin IV (Ang IV) also possess biological functions. These peptides are formed via the activity of several aminopeptidases. This review will briefly summarize what is known about gender differences in RAS-regulating aminopeptidase activities, their relationship with sex hormones, and their potential role in controlling blood pressure acting through local and circulating RAS.


RAS Angiotensinase Gender differences Sex hormones 


  1. 1.
    Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL, Jones DW, Materson BJ, Oparil S, Wright JT, Rocella EI (2003) The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 289:2560–2572PubMedGoogle Scholar
  2. 2.
    Chobanian AV, Bakris GL, Black HR et al (2003) A National High Blood Pressure Education Program Coordinating Committee, Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. Hypertension 42:1206–1252PubMedGoogle Scholar
  3. 3.
    Elliot WJ (2007) Systemic hypertension. Curr Probl Cardiol 32:201–259Google Scholar
  4. 4.
    Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223PubMedGoogle Scholar
  5. 5.
    Hoyer DL, Heron M, Murphy SL et al (2006) Deaths: final data for 2003. www.cdc.gov/nchs/products/pubs/pubd/hestats/finaldeaths03/finaldeaths03.htm
  6. 6.
    Thom T, Haase N, Rosamond W et al (2006) Heart disease and stroke statistics -2006 update: a report from the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation 113:85–151Google Scholar
  7. 7.
    MacMahon S, Neal B, Rodgers A (2005) Hypertension-time to move on. Lancet 365:1108–1109PubMedGoogle Scholar
  8. 8.
    Burt VL, Cutler JA, Higgings M, Horan MJ, Labarthe D, Whelton P, Brown C, Rocella EJ (1991) Trends in the prevalence awareness, treatment, and control of hypertension in the adult US population. Data from the health examination surveys, 1960 to 1991. Hypertension 26:60Google Scholar
  9. 9.
    Staessen J, Fagard R, Lijnen P, Thijs L, van Hoof R, Amery A (1990) Reference values for ambulatory blood pressure: a meta-analysis. J Hypertens Suppl 8:S57–64PubMedGoogle Scholar
  10. 10.
    Wiinberg N, Hoegholm A, Christensen HR, Bang LE, Mikkelsen KL, Nielsen PE, Svendsen TL, Kampmann JP, Madsen NH, Bentzon MW (1995) 24-h ambulatory blood pressure in 352 normal Danish subjects, related to age and gender. Am J Hypertens 8:978–986PubMedGoogle Scholar
  11. 11.
    Khoury S, Yarows SA, O’Brien TK, Sowers JR (1992) Ambulatory blood pressure monitoring in a nonacademic setting. Effects of age and sex. Am J Hypertens 5:616–623PubMedGoogle Scholar
  12. 12.
    Reckelhoff JF, Zhang H, Granger JP (1998) Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 31:435–439PubMedGoogle Scholar
  13. 13.
    Reckelhoff JF, Zhang H, Srivastava K (2000) Gender differences in development of hypertension in spontaneously hypertensive rats: role of the renin-angiotensin system. Hypertension 35:480–483PubMedGoogle Scholar
  14. 14.
    Masubuchi Y, Kumai T, Uematsu A, Komoriyama K, Hirai M (1982) Gonadectomy-induced reduction of blood pressure in adult spontaneously hypertensive rats. Acta Endocrinol 101:154–160PubMedGoogle Scholar
  15. 15.
    Chen YF, Meng QC (1991) Sexual dimorphism of blood pressure in spontaneously hypertensive rats is androgen dependent. Life Sci 48:85–96PubMedGoogle Scholar
  16. 16.
    Crofton JT, Ota M, Share L (1993) Role of vasopressin, the renin-angiotensin system and sex in Dahl salt-sensitive hypertension. J Hypertens 11:1031–1038PubMedGoogle Scholar
  17. 17.
    Rowland NE, Fregly MJ (1992) Role of gonadal hormones in hypertension in the Dahl salt-sensitive rat. Clin Exp Hypertens 14:367–375Google Scholar
  18. 18.
    Ouchi Y, Share L, Crofton JL, Iitake K, Brooks DP (1987) Sex difference in the development of deoxycorticosterone-salt hypertension in the rat. Hypertension 9:172–177PubMedGoogle Scholar
  19. 19.
    Ashton N, Balment RJ (1991) Sexual dimorphism in renal function and hormonal status of New Zealand genetically hypertensive rats. Acta Endocrinol 124:91–97PubMedGoogle Scholar
  20. 20.
    De la Chica S, Cortés P, Ramirez-Exposito MJ, Arias de Saavedra JM, Sanchez-Agesta R, Perez MC, Martinez-Martos JM (2007) In vivo administration of doxazosin in rats highly decreases serum circulating levels of testosterone through a mechanism involving testicular renin-angiotensin system. Int J Androl 15 doi:10.1111/j.1365-2605.2007.00771.x
  21. 21.
    Cheung BMY, Ong KL, Man YB et al (2006) Prevalence, awareness, treatment and control of hypertension: United States National Health and Nutrition Examination Survey, 2001–2002. J Clin Hypertens 8:93–98Google Scholar
  22. 22.
    Hajj I, Kotchen TA (2003) Trends in prevalence, awareness, treatment and control of hypertension in the United States, 1988–2000. JAMA 290:199–203Google Scholar
  23. 23.
    Sjöberg L, Kaaja R, Tuomilehto J (2004) Epidemiology of postmenopausal hypertension. Int J Pract Suppl 139:4–12Google Scholar
  24. 24.
    Braun-Menendez E, Fasciolo JC, Leloir LF, Muñoz JM (1940) The substance causing renal hypertension. J Physiol (London) 98:283–298Google Scholar
  25. 25.
    Page IH, Helmer OM (1940) A crystalline pressor substance (angiotensin) resulting from the reaction between renin and renin activator. J Exp Med 71:29–31PubMedGoogle Scholar
  26. 26.
    Ganten D, Schelling P, Vecsei P, Ganten U (1976) Isorenin of extrarenal origin. Am J Med 60:760–772PubMedGoogle Scholar
  27. 27.
    Guidelines Subcommittee (1999) The 1999 World Health Organization-International Society of Hypertension Guidelines for the Management of Hypertension. J Hypertens 17:151–183Google Scholar
  28. 28.
    Ward R (1990) Hypertension, pathophysiology, diagnosis and management. Raven Press, New York, pp 81–100Google Scholar
  29. 29.
    Hermansen K (2000) Diet, blood pressure and hypertension. Br Nutr 83:S113–119Google Scholar
  30. 30.
    Stamler J, Rose G, Stamler R, Elliot P, Dyer A, Marmot M (1989) INTERSALT study findings: public health and medical care implications. Hypertension 14:570–577PubMedGoogle Scholar
  31. 31.
    Rubattu S, Volpe M, Enea I, Russo R, Romano M, Trimarco B (1993) Influence of hypercholesterolemia on adrenal steroid metabolism and electrolyte balance in spontaneously hypertensive rats. Endocrinology 133:2015–2021PubMedGoogle Scholar
  32. 32.
    Bravo E, Ortu G, Cantafora A, Lambert MS, Avella M, Mayes PA, Botham KM (1995) Comparison of the hepatic uptake and processing of cholesterol from chylomicrons of different fatty acid composition in the rat in vivo. Biochim Biophys Acta 1258:328–336PubMedGoogle Scholar
  33. 33.
    Pomposiello SI, Alva M, Wilde DW, Carretero OA (1998) Linoleic acid induces relaxation and hyperpolarization of the pig coronary artery. Hypertension 31:615–620PubMedGoogle Scholar
  34. 34.
    Genest J, Cantin M, Garcia R, Thibault G, Gutkowska F (1983) Extrarenal angiotensin forming enzyme. Clin Exp Hypertens 5:1065–1080Google Scholar
  35. 35.
    Johnston CI (1990) Biochemistry and pharmacology of the renin-angiotensin system. Drugs 39:21–31PubMedGoogle Scholar
  36. 36.
    Dina R, Jafari M (2000) Angiotensin II-receptor antagonist-an overview. Am J Health Syst Pharm 57:1231–1241PubMedGoogle Scholar
  37. 37.
    Kim S, Iwao H (2000) Molecular and cellular mechanism of angiotensin II mediated cardiovascular and renal diseases. Pharmacol Rev 52:11–34PubMedGoogle Scholar
  38. 38.
    Bohlen O, Halbach O (2003) Angiotensin IV in the central nervous system. Cell Tissue Res 311:1–9Google Scholar
  39. 39.
    Dzau VJ (1988) Cardiac renin-angiotensin system: molecular and functional aspects. Am J Med 84:22–27PubMedGoogle Scholar
  40. 40.
    Martinez-Martos JM, Ramirez-Exposito MJ (2006) Dietary fat and hypertension: a novel approach through the proteolytic regulatory enzymes of the renin-angiotensin-system. Cardiovasc Hematol Agents Med Chem 4:263–276PubMedGoogle Scholar
  41. 41.
    Wright JW, Harding JW (1997) Important roles for angiotensin III and IV in the brain renin-angiotensin system. Brain Res Rev 25:96–124PubMedGoogle Scholar
  42. 42.
    Wright JW, Reichert JR, Davis CJ, Harding JW (2002) Neuronal plasticity and the brain renin-angiotensin system. Neurosci Biobehav Rev 26:529–552PubMedGoogle Scholar
  43. 43.
    Kehoe PG (2003) The renin-angiotensin-aldosterone system and Alzheimer’s disease. J Renin Angiotensin Aldosterone Syst 4:80–93PubMedGoogle Scholar
  44. 44.
    Hilchey SD, Bell-Quilley CP (1995) Association between the natriuretic action of angiotensin (1–7) and selective stimulation of renal prostaglandin I2 release. Hypertension 25:1238–1244PubMedGoogle Scholar
  45. 45.
    Ferrario CM, Chappell MC, Tallant EA, Bronihan KB, Diz DI (1997) Counterregulatory actions of angiotensin (1–7). Hypertension 30:535–541PubMedGoogle Scholar
  46. 46.
    Radhakrishnan R, Sim MK (1995) Actions of D-amino acid-substituted analogues of des-Asp-angiotensin I on the central pressor action of angiotensin III. Eur J Pharmacol 294:337–339PubMedGoogle Scholar
  47. 47.
    Saavedra JM (1992) Brain and pituitary angiotensin. Endocr Rev 13:329–380PubMedGoogle Scholar
  48. 48.
    Unger T, Badoer E, Ganten D, Lang EE, Retting R (1988) Brain angiotensin: pathways and pharmacology. Circulation 77:140–154Google Scholar
  49. 49.
    Blair-West JR, Coghlan JP, Denton DA, Funder JW, Scoggins BA, Wright RD (1971) The effects of the heptapeptide (2–8) and hexapeptide (3–8) fragments of angiotensin II on aldosterone secretion. J Clin Endocrinol Metab 32:575–578PubMedGoogle Scholar
  50. 50.
    Sim MK, Radhkrishnan R (1994) Novel central action of des-Asp-angiotensin I. Eur J Pharmacol 257:R1–3PubMedGoogle Scholar
  51. 51.
    Lodja Z, Gossrau R (1980) Study on aminopeptidase A. Histochemistry 67:237–290Google Scholar
  52. 52.
    Wright JW, Harding JW (1995) Brain angiotensin receptor subtypes AT1, AT2 and AT4 and their functions. Regul Pept 59:269–295PubMedGoogle Scholar
  53. 53.
    McDonald JK, Barret AJ (1986) Mammalian proteases, a glossary and bibliography, vol 2: exopeptidases. New York: Academic Press, pp 23–100Google Scholar
  54. 54.
    Cheung HS, Cushman DW (1971) A soluble aspartate aminopeptidase from dog kidney. Biochim Biophys Acta 242:190–193PubMedGoogle Scholar
  55. 55.
    Martinez JM, Prieto I, Ramirez MJ, Gasparo M, Hermoso F, Arias JM, Alba F, Ramirez M (1998) Sex differences and age-related changes in human serum aminopeptidase A activity. Clin Chim Acta 274:53–61PubMedGoogle Scholar
  56. 56.
    Sanderink GJ, Artur Y, Schiele F et al (1988) Alanine aminopeptidase in serum: biological variations and reference limits. Clin Chem 34:1422–1426PubMedGoogle Scholar
  57. 57.
    Rowland M, Roberts J (1982) NCHS advance data No. 84. Vital and Health Statistics of the National Center for Health Statistics, Oct 8, 1982. US Department of Health and Human Services, Washington, DC, 11 ppGoogle Scholar
  58. 58.
    Michel JB, Heudes D, Michel O (1994) Effects of chronic Ang I-converting enzyme inhibition on ageing processes. II. Large arteries. Am J Physiol 267:124–135Google Scholar
  59. 59.
    Duggan J, Nussberger J, Kilfeather S et al (1993) Aging and human hormonal and pressor responsiveness to angiotensin II infusion with simultaneous measurement of exogenous and endogenous angiotensin II. Am J Hypertens 6:641–647PubMedGoogle Scholar
  60. 60.
    Meade TW, Imeson JD, Gordon D et al (1983) The epidemiology of plasma renin. Clin Sci 64:273–280PubMedGoogle Scholar
  61. 61.
    Van Acker KJ, Scharpe SL, Deprettere AJR (1979) Renin-angiotensin-aldosterone system in the healthy infant and child. Kidney Int 16:196–203PubMedGoogle Scholar
  62. 62.
    Duggan J, Kildeather D, O’Brien E (1992) Effects of ageing and hypertension on plasma angiotensin II and platelet angiotensin II receptor density. Am J Hypertens 5:687–693PubMedGoogle Scholar
  63. 63.
    Jung YS, Lee S, Shin HS (1996) Effects of age on angiotensin II response and antagonistic activity of losartan in rat aorta and liver. Arch Pharmacol Res 19:462–468CrossRefGoogle Scholar
  64. 64.
    Martinez JM, Prieto I, Ramirez MJ et al (1997) Cholesterol and steroids action on aminopeptidases. Biochem Soc Trans 25:113SPubMedGoogle Scholar
  65. 65.
    Oparil S, Miller AP (2005) Gender and blood pressure. J Clin Hypertens 7:300–309Google Scholar
  66. 66.
    Rekelhoff JF, Zhang H, Granges JP (1998) Testosterone exacerbates hypertension and reduces pressure-natriuresis in male spontaneously hypertensive rats. Hypertension 31:435–439Google Scholar
  67. 67.
    Pechere-Bertschi A, Burnier M (2004) Female sex hormones, salt and blood pressure regulation. Am J Hypertens 17:994–1001PubMedGoogle Scholar
  68. 68.
    Rubanyi GM, Johns A, Kauser K (2002) Effects of estrogen on endothelial function and angiogenesis. Vasc Pharmacol 38:89–98Google Scholar
  69. 69.
    Kon Y (1996) Local renin-angiotensin system: specially in coagulating glands of mice. Arch Histol Cytol 59:399–420PubMedGoogle Scholar
  70. 70.
    Vila-Porcile E, Corvol P (1988) Angiotensinogen, prorenin and renin are co-localized in the secretory granules of all glandular cells of the rat anterior pituitary: an immunoultrastructural study. J Histochem Cytochem 46:301–311Google Scholar
  71. 71.
    Deschepper CF, Mellon SH, Cumming F, Baxter JD, Ganong WF (1986) Analysis by immunocytochesmistry and in-situ hybridisation of renin and its mRNA in kidney, testis, adrenal and pituitary of the rat. Proc Natl Acad Sci USA 83:7552–7556PubMedGoogle Scholar
  72. 72.
    Mulrow PJ (1993) The adrenal cortical renin-angiotensin system. In: Robertson JIS, Nicholls MS (eds) The renin angiotensin system. Gower Medical Publishing, London, pp 1–9Google Scholar
  73. 73.
    Wright JW, Krebs LT, Stobb JW, Harding JW (1995) The angiotensin IV system: functional implications. Front Neuroendocrinol 16:23–52PubMedGoogle Scholar
  74. 74.
    Volpe M, Gigante B, Enea I, Porcellini A, Russo R, Lee MA, Magri P, Condorelli G, Savoia C, Lindpaintner K, Rubattu S (1997) Role of tissue renin in the regulation of aldosterone biosynthesis in the adrenal cortex of nephrectomized rats. Circ Res 85:857–864Google Scholar
  75. 75.
    Barret AJ, Rawlings ND (1998) Handbook of proteolytic enzymes. Academic Press, LondonGoogle Scholar
  76. 76.
    Ardaillou R (1997) Active fragment of AngII: enzymatic pathways of synthesis and biological effects. Curr Opin Nephrol Hypertens 6:8–34Google Scholar
  77. 77.
    Wzczepanska-Sadowska E (1996) Interaction of vasopressin and Ang II in the central control of blood pressure and thirst. Regul Pept 66:65–71Google Scholar
  78. 78.
    Garcia MJ, Martinez-Martos JM, Mayas MD, Carrera P, Ramirez-Exposito MJ (2003) Hormonal status modifies renin-angiotensin system-regulating aminopeptidases and vasopressin-degrading activity in the hypothalamus-pituitary-adrenal-axis of male mice. Life Sci 73:525–538PubMedGoogle Scholar
  79. 79.
    Ganong WF, Murakami K (1987) The role of angiotensin II in the regulation of ACTH secretion. Ann N Y Acad Sci 512:176–186PubMedGoogle Scholar
  80. 80.
    Zini S, Fournier-Zaluski MC, Chauvel E, Roques BP, Corvol P, Llorens-Cortes C (1996) Identification of metabolic pathways of brain angiotensin II and III using specific aminopeptidase inhibitors: predominant role of angiotensin III in the control of vasopressin release. Proc Natl Acad Sci USA 93:11968–11973PubMedGoogle Scholar
  81. 81.
    Zini S, Demassey Y, Fournier-Zaluski MC, Bischoff L, Corvol P, Llorens-Cortes C, Sanderson C (1998) Inhibition of vasopressinergic neurons by central injection of a specific aminopeptidase A inhibitor. Neuroreport 9:825–828PubMedGoogle Scholar
  82. 82.
    Lenkey Z, Palkovits M, Corvol P, Llorens-Cortes C (1997) Expression of angiotensin type-1 (AT1) and type-2 (AT2) receptor mRNA in the adult rat brain: a functional neuroanatomical review. Front Neuroendocrinol 18:383–439Google Scholar
  83. 83.
    Swanson GN, Hanesworth JM, Sardinia MF, Coleman JK, Wright JW, Hall KL, Miller-Wing AV, Stobb JW, Cook VI, Harding EC, Harding JW (1992) Discovery of a distinct binding site for angiotensin II (3-8), a putative angiotensin IV receptor. Regul Pept 40:409–419PubMedGoogle Scholar
  84. 84.
    Haas DA, George SR (1988) Gonadal regulation of corticotropin-releasing factor immunoreactivity in hypothalamus. Brain Res Bull 20:361–367PubMedGoogle Scholar
  85. 85.
    Handa RJ, Nunley KM, Lorens SA, Louie JP, McGivern RF, Bollnow MR (1994) Androgen regulation of adrenocorticotropin and corticosterone secretion in the male rat following novelty and foot shock stressors. Physiol Behav 55:117–124PubMedGoogle Scholar
  86. 86.
    Viau V, Meaney MJ (1996) The inhibitory effect of testosterone on hypothalamic-pituitary-adrenal responses to stress is mediated by the medial preoptic area. J Neurosci 16:1866–1876PubMedGoogle Scholar
  87. 87.
    Viau V, Chu A, Soriano L, Dallman MF (1999) Independent and overlapping effects of corticosterone and testosterone on corticotropin-releasing hormone and arginine vasopressin mRNA expression in the paraventricular nucleus of the hypothalamus and stress-induced adrenocorticotropic hormone release. J Neurosci 16:6684–6693Google Scholar
  88. 88.
    Ganong WF (1989) Angiotensin II in the brain and pituitary: contrasting roles in the regulation of adenohypophyseal secretion. Horm Res 31:24–31PubMedGoogle Scholar
  89. 89.
    Leniewska B, Nowak M, Malendowicz LK (1990) Sex differences in adrenocortical structure and function. XXVIII. ACTH and corticosterone in intact gonadectomised and gonadal hormone replaced rats. Horm Metab Res 22:378–381Google Scholar
  90. 90.
    Lumbers ER (1999) Angiotensin and aldosterone. Regul Pept 80:91–100PubMedGoogle Scholar
  91. 91.
    Roy BN, Reid RL, Van Vugt DA (1999) The effects of estrogen and progesterone on corticotropin-releasing hormone and arginine vasopressin messenger ribonucleic acid levels in the paraventricular nucleus and supraoptic nucleus of the rhesus monkey. Endocrinology 140:2191–2198PubMedGoogle Scholar
  92. 92.
    Viau V, Meany MJ (1991) Variations in the hypothalamic-pituitary-adrenal response to stress during the estrous cycle in the rat. Endocrinology 129:2503–2511PubMedGoogle Scholar
  93. 93.
    Burguess LM, Handa R (1992) Chronic estrogen-induced alterations in adrenocorticotropin and corticosterone secretion, and glucocorticoid receptor-mediated functions in female rats. Endocrinology 131:1261–1269Google Scholar
  94. 94.
    Bohler HC, Zoeller RT, King JC, Rubin BS, Weber R, Merrian GR (1990) Corticotropin releasing hormone mRNA is elevated on the afternoon of proestrus in the parvocellular paraventricular nuclei of the female rat. Brain Res Mol Brain Res 8:259–262PubMedGoogle Scholar
  95. 95.
    Kitay JI (1963) Effects of testosterone on pituitary corticotrophin and adrenal steroid secretion in male and female rats. Acta Endocrinol 43:601–608PubMedGoogle Scholar
  96. 96.
    Coyne MD, Kitay JI (1971) Effects of orchiectomy on pituitary secretion of ACTH. Endocrinology 8/9:1024–1028Google Scholar
  97. 97.
    Raasch W, Wittmershaus C, Dendorfer A, Voges I, Pahlke F, Dodt C, Dominiak P, Jöhren O (2006) Angiotensin II inhibition reduces stress sensitivity of hypothalamo-pituitary-adrenal axis in SHR. Endocrinology 147:3539–3546PubMedGoogle Scholar
  98. 98.
    Hinojosa-Laborde C, Lange DL, Haywood JR (2000) Role of female sex hormones in the reversal of Dahl salt-sensitive hypertension. Hypertension 35:484–489PubMedGoogle Scholar
  99. 99.
    Crofton JT, Share L (1997) Gonadal hormones modulate doxycorticosterone-salt hypertension in male and female rats. Hypertension 29:494–499PubMedGoogle Scholar
  100. 100.
    Brosnihan KB, Weddle D, Anthony MS, Heise C, Li P, Ferrario CM (1997) Effects of chronic hormone replacement on the renin-angiotensin system in cynomolgus monkeys. J Hypertens 15:719–726PubMedGoogle Scholar
  101. 101.
    Seltzer A, Pinto SE, Viglione PN, Correa FM, Libertum C, Tsutsumi K, Steele MK, Saavedra JM (1992) Estrogens regulate angiotensin-converting enzyme and angiotensin receptor in female rat anterior pituitary. Neuroendocrinology 55:460–467PubMedGoogle Scholar
  102. 102.
    Tanaka M, Nayaka S, Wantanabe M, Kumai T, Tateishi T, Kobayashi S (1997) Effect of ovariectomy and estrogen replacement in aorta ACE in rats. Jpn J Pharmacol 73:361–363PubMedGoogle Scholar
  103. 103.
    Carriere S (1986) Chronic estradiol treatment decreases angiotensin II receptor density in the anterior pituitary gland and adrenal cortex by not in the mesenteric artery. Neuroendocrinology 43:49–56PubMedGoogle Scholar
  104. 104.
    Krishnamurthy K, Verbalis JG, Zheng W, Wu Z, Clerch LB, Sandberg K (1999) Estrogen regulates angiotensin AT1 receptor expression via cytosolic protein that bind to the 5’ leader sequence of the receptor mRNA. Endocrinology 140:5435–5438Google Scholar
  105. 105.
    Chen FM, Printz MP (1983) Chronic estrogen treatment reduces angiotensin II receptors in anterior pituitary. Endocrinology 113:1503–1510PubMedGoogle Scholar
  106. 106.
    Nickenig G, Baumer AT, Grohe C, Kahlert S, Strehlow K, Rosenkranz S, Stablein A, Beckers F, Smits JF, Daemen MJ, Better H, Bohm M (1998) Estrogen modulates At1 receptor gene expression in vitro and in vivo. Circulation 97:2197–2201PubMedGoogle Scholar
  107. 107.
    Roesch D, Tian Y, Zheng W, Shi M, Verbalis JG, Sandberg K (2000) Estrogen attenuates angiotensin-induced aldosterone secretion in ovariectomized rats. Endocrinology 141:4629–4636PubMedGoogle Scholar
  108. 108.
    Najletti A, Masson GM (1972) Studies on angiotensinogen formation in a liver perfusion system. Circ Res 30:187–202Google Scholar
  109. 109.
    Chang E, Perlman A (1987) Multiple hormones regulate angiotensinogen messenger ribonucleic acid levels in a rat hepatome cell line. Endocrinology 121:513–519PubMedGoogle Scholar
  110. 110.
    Kunapul S, Benedict C, Kumar A (1987) Tissue specific hormonal regulation of the rat angiotensinogen gene expression. Arch Biochem Biophys 254:642–646Google Scholar
  111. 111.
    Brosnihan K, Li P, Ganten D, Ferrario C (1997) Estrogen protects transgenic hypertension rats by shifting the vasoconstrictor-vasodilator balance of RAS. Am J Physiol 273:R1908–R1915PubMedGoogle Scholar
  112. 112.
    Hinojosa-Laborde C, Craig T, Zheng W, Ji H, Haywood JR, Sandberg K (2004) Ovariectomy augments hypertension in aging female Dahl salt sensitive rats. Hypertension 44:405–409PubMedGoogle Scholar
  113. 113.
    Marks LS, Partin AW, Dorey FG, Gomley GJ, Epstein JL, Garris HB, Macairan M, Shery ED, Santos PB, Stoner E, deKernion JB (1999) Long term effects of finasteride on prostate tissue composition. Urology 53:574–580PubMedGoogle Scholar
  114. 114.
    Speth RC, Bumpus FM, Husain A (1986) Identification of angiotensin II receptors in the rat ovary. Eur J Pharmacol 130:351–352PubMedGoogle Scholar
  115. 115.
    Husain A, Bumpus FM, De Silva P, Speth RC (1987) Localization of angiotensin II receptors in ovarian follicles and the identification of angiotensin II in rat ovaries. Proc Natl Acad Sci USA 84:2489–2493PubMedGoogle Scholar
  116. 116.
    Pepperell JR, Nemeth G, Yamada Y, Naftolin F (1993) The type 1 angiotensin-II receptor mediates intracellular calcium mobilization in rat luteal cells. Endocrinology 133:1678–1684PubMedGoogle Scholar
  117. 117.
    Pepperell JR, Nemeth G, Yamada Y, Naftolin F, Merino M (2006) Localized accumulation of angiotensin II and production of angiotensin (1–7) in rat luteal cells, and effects on steroidogenesis. Am J Physiol Endocrinol Metab 291:221–233Google Scholar
  118. 118.
    Schultze D, Brunswig B, Mukhopadhyay AK (1993) Renin and prorenin-like activities in bovine ovarian follicles. Endocrinology 133:1678–1684Google Scholar
  119. 119.
    Speth RC, Husain A (1988) Distribution of angiotensin-converting enzyme and angiotensin II-receptor binding sites in the rat ovary. Biol Reprod 38:695–702PubMedGoogle Scholar
  120. 120.
    Kuo TC, Endo K, Dharmarajan AM, Miyazaki T, Atlas SJ, Wallach EE (1991) Direct effect of angiotensin II on in vitro perfused rabbit ovary. J Reprod Fertil 92:469–474PubMedCrossRefGoogle Scholar
  121. 121.
    Yoshimura Y, Karube M, Koyama N, Shiokawa S, Nanno T, Nakana Y (1992) Angiotensin II directly induces follicle rupture and oocyte maturation in the rabbit. FEBS Lett 307:305–308PubMedGoogle Scholar
  122. 122.
    Yoshimura Y, Karube M, Aoki H, Oda T, Koyama N, Nagai A et al (1996) Angiotensin II induces ovulation and oocyte maturation in rabbit ovaries via the AT2 receptor subtype. Endocrinology 137:1204–1211PubMedGoogle Scholar
  123. 123.
    Parmentier M, Inagami T, Pochet R, Desclin JC (1983) Pituitary-dependent renin-like immunoreactivity in rat testes. Endocrinology 112:1318–1323PubMedGoogle Scholar
  124. 124.
    Naruse K, Murakoshi M, Osamura RY, Naruse M, Toma H, Watanabe K, Demura H, Inagami T, Shizume K (1985) Immunohistological evidence for renin in human endocrine tissues. J Clin Endocrinol Metab 61:172–177PubMedGoogle Scholar
  125. 125.
    Pandey KN, Misono KS, Inagami T (1984) Evidence for intracellular formation of angiotensins: coexistence of renin and angiotensin-converting enzyme in Leydig cell of rat testis. Biochem Biophys Res Commun 122:1337–1343PubMedGoogle Scholar
  126. 126.
    Pandey KN, Inagami T (1986) Regulation of renin angiotensins by gonadotropic hormones in cultured murine Leydig tumor cells. Release of angiotensin but not renin. J Biol Chem 261:3934–3938PubMedGoogle Scholar
  127. 127.
    Velletri PA (1985) Testicular angiotensin I-converting enzyme (E.C. Life Sci 36:1597–1608PubMedGoogle Scholar
  128. 128.
    Velletri PA, Aquilano DR, Bruckwick E, Tsai-Morris CH, Dufau ML, Lovenberg W (1985) Endocrinological control and cellular localization of rat testicular angiotensin-converting enzyme (EC Endocrinology 116:2516–2522PubMedCrossRefGoogle Scholar
  129. 129.
    Douglas GC, O’Bryan MK, Hedger MP, Lee DK, Yarski MA, Smith AI, Lew RA (2004) The novel angiotensin-converting enzyme (ACE) homolog, ACE2, is selectively expressed by adult Leydig cells of the testis. Endocrinology 145:4703–4711PubMedGoogle Scholar
  130. 130.
    Khanum A, Dufau ML (1988) Angiotensin II receptors and inhibitory actions in Leydig cells. J Biol Chem 263:5070–5074PubMedGoogle Scholar
  131. 131.
    Adahi EY, Hsueh AJ (1981) Stimulation of beta 2-adrenergic responsiveness by follicle-stimulating hormone in rat granulosa cells in vitro and in vivo. Endocrinology 108:2170–2178Google Scholar
  132. 132.
    Aguado LI, Petrovic SL, Ojeda SR (1982) Ovarian beta-adrenergic receptors during the onset of puberty: characterization, distribution and coupling to steroidogenic responses. Endocrinology 110:1124–1132PubMedGoogle Scholar
  133. 133.
    Hernandez ER, Jimenez JL, Payne DW, Adashi EY (1988) Adrenergic regulation of ovarian androgen biosynthesis is mediated via beta 2-adrenergic theca-interstitial cell recognition sites. Endocrinology 122:1592–1602PubMedGoogle Scholar
  134. 134.
    Webley GE, Luck MR, Hearn JP (1988) Stimulation of progesterone secretion by cultured human granulosa cell with melatonin and catecholamines. J Reprod Fertil 84:669–677PubMedCrossRefGoogle Scholar
  135. 135.
    Bodis J, Bognar Z, Hartmann G, Torok A, Csaba IF (1992) Measurement of noradrenaline, dopamine and serotonin contents in follicular fluid of human graafian follicles after superovulation treatment. Gynecol Obstet Invest 33:165–167PubMedCrossRefGoogle Scholar
  136. 136.
    Fohr KJ, Mayerhofer A, Sterzik K, Rudolf M, Rosenbusch B, Gratzl M (1993) Concerted action of human chorionic gonadotropin and norepinephrine on intracellular-free calcium in human granulosa-lutein cells: evidence for the presence of a functional alpha-adrenergic receptor. J Clin Endocrinol Metab 76:367–373PubMedGoogle Scholar
  137. 137.
    Wasilewska-Dziubinska E, Borewiec M, Chmilowska M, Wolinska-Witort E, Baranowska B (2002) Alfa 1 adrenergic potentiation of progesterone accumulation stimulated by vasoactive intestinal peptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) in cultured rat granulosa cell. Neuro Endocrinol Lett 23:141–148PubMedGoogle Scholar
  138. 138.
    Mayerhofer A, Bartke A, Steger RW (1989) Catecholamine effects of testicular testosterone production in the gonadally active and the gonadally regressed adult golden hamster. Biol Reprod 40:752–761PubMedGoogle Scholar
  139. 139.
    Mayenhofer A, Stegerm RW, Gow G, Bartke A (1992) Catecholamines stimulate testicular testosterone release of the immature golden hamster via interaction with alpha- and beta-adrenergic receptors. Acta Endocrinol 127:526–530Google Scholar
  140. 140.
    Bumpus FM, Pucell AG, Daud AI, Husain A (1988) Angiotensin II: an intraovarian regulatory peptide. Am J Med Sci 295:406–408PubMedGoogle Scholar
  141. 141.
    Pucell AG, Bumpus FM, Husain A (1987) Rat ovarian angiotensin II receptors. Characterization and coupling to estrogen secretion. J Biol Chem 262:7076–7080PubMedGoogle Scholar
  142. 142.
    Li XM, Juorio AV, Murphy BD (1995) Angiotensin II interferes with steroidogenesis in porcine granulosa cells. Biol Reprod 53:791–799PubMedGoogle Scholar
  143. 143.
    Reaux A, Fournie-Zaluski MC, Llorens-Cortes C (2001) Angiotensin III: a central regulator of vasopressin release and blood pressure. Trends Endocrinol Metab 12:157–162PubMedGoogle Scholar
  144. 144.
    Chansel D, Czekalski S, Vandermeersch S, Ruffer E, Fournie-Zaluski MC, Ardaillou R (1998) Characterization of angiotensin IV-degrading enzymes and receptors on rat mesangial cells. Am J Physiol 275:F535–542PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • María Jesús Ramírez-Expósito
    • 1
  • José Manuel Martínez-Martos
    • 1
  1. 1.Experimental and Clinical Physiopathology Research Group, Department of Health Sciences/Physiology, Faculty of Experimental and Health SciencesUniversity of JaénJaenSpain

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