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Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids

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Endothelial Mechanisms of Vasomotor Control

Summary

As a source of several vasoactive factors, the endothelium takes part in the regulation of vascular tone. The most important endothelium-derived vasoactive substances are nitric oxide, prostacyclin, endothelin-1 and contracting factors requiring the activity of cyclooxygenase. The endothelium is an obvious target organ of cardiovascular risk factors. Accordingly, functional alterations do occur with aging, hypertension, and lipids. All three conditions are associated with a decreased basal and stimulated release of endothelium-derived nitric oxide. On the other hand, the release of endothelin-1 appears to increase with age, while the sensitivity to the peptide markedly decreases under the same conditions. In the spontaneously hypertensive rat, acetylcholine and stretch evoke the release of cyclooxygenase-dependent endothelium-derived contracting factor, most likely prostaglandin H2. The sensitivity and circulating levels of endothelin-1, on the other hand, are reduced in this experimental model of hypertension. In the porcine coronary circulation, oxidized low-density lipoproteins selectively reduce endothelium-dependent relaxations to aggregating platelets, serotonin, and thrombin which are mediated by nitric oxide. The alterations of endothelial function occurring with aging, hypertension, and hyperlipidemia may have important clinical implications for the pathogenesis of cardiovascular disease.

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References

  1. Amstein R, Fetkovska N, Lüscher TF, Kiowski W, Bühler FR (1988) Age and the platelet serotonin vasoconstrictor axis in essential hypertension. J Cardiovasc Pharmacol 11 (Suppl 1):35–40

    Article  Google Scholar 

  2. Andrews HE, Bruckdorfer KR, Dunn RC, Jacobs M (1987) Low-density lipoproteins inhibit endothelium-dependent relaxation in rabbit aorta. Nature 327:237–239

    Article  PubMed  CAS  Google Scholar 

  3. Badouin-Legros M, Dard B, Guicheney P (1986) Hyperreactivity of platelets from spontaneously hypertensive rats. Hypertension 8:694–699

    Google Scholar 

  4. Boulanger C, Bühler FR, Lüscher TF (1989) Low density lipoproteins impair the release of endothelium-derived relaxing factor from cultured porcine endothelial cells (abstract). Eur Heart J 10:331

    Google Scholar 

  5. Boulanger C, Hendrickson H, Lorenz RR, Vanhoutte PM (1989) Release of different relaxing factors by cultured porcine endothelial cells. Circ Res 64:1070–1078

    PubMed  CAS  Google Scholar 

  6. Boulanger C, Lüscher TF (1990) Release of endothelin from the porcine aorta: Inhibition by endothelium-derived nitric oxide. J Clin Invest 85:587–590

    Article  PubMed  CAS  Google Scholar 

  7. Brian SD, Crossman DC, Buckley TL, Williams TJ (1989) Endothelin-1: demonstration of potent effects on the microcirculation of humans and other species. J Cardiovasc Pharmacol 13 (Suppl 5):147–149

    Article  Google Scholar 

  8. Carvalho MHC, Scivoletto R, Fortes ZB, Nigro D, Cordellini S (1987) Reactivity of aorta and mesenteric microvessels to drugs in spontaneously hypertensive rats: role of the endothelium. J Hypertension 5:377–382

    Article  CAS  Google Scholar 

  9. Criscione L, Nellis P, Riniker B, Thomann H, Bürdet R (1989) Reactivity and sensitivity of mesenteric vascular beds and aortic rings of SH and WKY rats to endothelin: effect of calcium entry blockers. Br J Pharmacol 99:31–36

    Google Scholar 

  10. Davenport AP, Ashby MJ, Easton P, Ella S, Bedford K, Dickerson C, Nunez DJ, Capper SJ, Brown MJ (1990) A sensitive radioimmunoassay measuring endothelin-like immunoreactivity in human plasma: comparison of levels in patients with essential hypertension and normotensive control subjects. Clin Sci 78:261–264

    PubMed  CAS  Google Scholar 

  11. De Clerck F (1986) Blood platelets in human essential hypertension. Agents Actions 18:563–580

    Article  PubMed  Google Scholar 

  12. De Mey JG, Gray SD (1985) Endothelium-dependent reactivity in resistance vessels. Prog Appl Microcirc 88:181–187

    Google Scholar 

  13. Diederich D, Yang Z, Bühler FR, Lüscher TF (1989) Endothelium derived relaxing factor and endothelin in resistance arteries of hypertensive rats (abstract). J Vasc Med Biol 1/3:167–0

    Google Scholar 

  14. Diederich D, Yang Z, Bühler FR, Lüscher TF (1990) Impaired endothelium-dependent relaxations in hypertensive resistance arteries involve the cyclooxygenase pathway. Am J Physiol 258:H445–H451

    PubMed  CAS  Google Scholar 

  15. Dohi Y, Thiel MA, Bühler FR, Lüscher TF (1990) Activation of the endothelial L-arginine pathway in pressurized mesenteric resistance arteries: effect of age and hypertension. Hypertension 16:170–179

    PubMed  CAS  Google Scholar 

  16. Dohi Y, Lüscher TF (1990) Aging differentially affects direct and indirect actions of endothelin-1 in perfused mesenteric resistance arteries of the rat. Br J Pharmacol 100:889–893

    PubMed  CAS  Google Scholar 

  17. Dohi Y, Lüscher TF (1990) Hypertension differentially affects intra-and extraluminal activation of the endothelium (Abstract). Hypertension 6:315

    Google Scholar 

  18. Dudel C, Förstermann U (1988) Gossypol attenuates selectively the blood pressure lowering effect of endothelium-dependent vasodilators in the rabbit in vivo. Eur J Pharmacol 145:217–221

    Article  PubMed  CAS  Google Scholar 

  19. Emori T, Hirata Y, Aizawa T, Ando K, Shichiri M, Marumo F (1989) Plasma endothelin levels in patients with coronary artery disease undergoing percutaneous coronary angioplasty. Circulation 80 (Suppl II):22327–0

    Google Scholar 

  20. Fetkovska N, Amstein R, Ferracin F, Regenass M, Pletscher A, Bühler FR (1990) 5-hydroxy-tryptamine kinetics and activation of blood platelets in patients with essential hypertension. Hypertension 15:267–273

    PubMed  CAS  Google Scholar 

  21. Gray SD, De Mey JG (1985) Vascular reactivity in neonatal spontaneously hypertensive rats. Progr Appl Microcirc 8:173–180

    Google Scholar 

  22. Guicheney P, Legros M, Marcel D, Kamal L, Meyer P (1985) Platelet serotonin content and uptake in spontaneously hypertensive rats. Life Sci 36:679–685

    Article  PubMed  CAS  Google Scholar 

  23. Hynes MR, Duckies SP (1987) Effect of increasing age on the endothelium-mediated relaxation of rat blood vessels in vitro. J Pharmacol Exp Ther 241:387–392

    PubMed  CAS  Google Scholar 

  24. Hongo K, Nakagomi T, Kassell NF, Sasaki T, Lehmann M, Vollmer DG, Tsukahara T, Ogawa H, Torner J (1988) Effect of aging and hypertension on endothelium-dependent vascular relaxation in rat carotid artery. Stroke 19:892–897

    Article  PubMed  CAS  Google Scholar 

  25. Kato T, Iwama Y, Okumura K, Hashimoto H, Ito T, Satake T (1990) Prostaglandin H2 may be the endothelium-derived contracting factor released by acetylcholine in the aorta of the rat. Hypertension 15:475–481

    PubMed  CAS  Google Scholar 

  26. Koga T, Takata Y, Kobayashi K, Takishita S, Yamashita Y, Fujishima M (1989) Age and hypertension promote endothelium-dependent contractions to acetylcholine in the aorta of the rat. Hypertension 14:542–548

    PubMed  CAS  Google Scholar 

  27. Konishi M, Su C (1983) Role of endothelium in dilator responses of SHR arteries. Hypertension 5:881–886

    PubMed  CAS  Google Scholar 

  28. Kugiyama K, Kerns SA, Morrisett JD, Roberts R, Henry PD (1990) Impairment of endothelium-dependent arterial relaxation by lysolecithin in modified low-density lipoproteins. Nature 344:160–162

    Article  PubMed  CAS  Google Scholar 

  29. Linder L, Kiowski W, Bühler FR, Lüscher TF (1990) Indirect evidence of the release of endothelium-derived relaxing factor in human forearm circulation in vivo: blunted response in essential hypertension. Circulation 81:1762–1767

    Article  PubMed  CAS  Google Scholar 

  30. Kiowski W, Lüscher TF, Linder L, Bühler FR (1991) Endothelin-1-induced vasoconstriction in humans: reversal by calcium channel blockade but not by nitrovasodilators or endothelium-derived relaxing factor. Circulation 83:469–475

    PubMed  CAS  Google Scholar 

  31. Lockette WE, Otsuha Y, Carretero OA (1986) Endothelium-dependent relaxation in hypertension. Hypertension 8 (Suppl II):61–66

    Google Scholar 

  32. Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent responses to aggregating platelets and serotonin in spontaneously hypertensive rats. Hypertension 8 (Suppl II):55–60

    Google Scholar 

  33. Lüscher TF, Rubanyi GM, Aarhus LL, Vanhoutte PM (1986) Serotonin reduces coronary flow in isolated hearts of the SHR. J Hypertension 4 (Suppl 5):148–150

    Google Scholar 

  34. Lüscher TF, Romero JC, Vanhoutte PM (1986) Bioassay of endothelium-derived vasoactive substances in the aorta of normotensive and spontaneously hypertensive rats. J Hypertension 4 (Suppl 6):81–83

    Google Scholar 

  35. Lüscher TF, Vanhoutte PM (1986) Endothelium-dependent contractions to acetylcholine in the aorta of the SHR. Hypertension 8:344–348

    PubMed  Google Scholar 

  36. Lüscher TF, Vanhoutte PM, Raij L (1987) Antihypertensive therapy normalizes endothelium-dependent relaxations in salt-induced hypertension of the rat. Hypertension 9 (Suppl III):193–197

    Google Scholar 

  37. Lüscher TF, Raij L, Vanhoutte PM (1987) Effect of hypertension and its reversal on endothelium-dependent relaxations in the rat aorta. J Hypertension 5 (Suppl 5):153–155

    Google Scholar 

  38. Lüscher TF, Raij L, Vanhoutte PM (1987) Endothelium-dependent responses in normotensive and hypertensive Dahl rats. Hypertension 9:157–163

    PubMed  Google Scholar 

  39. Lüscher TF, Diederich D, Vanhoutte PM, Weber E, Bühler FR (1988) Endothelium-dependent responses in the common carotid and renal artery of normotensive and spontaneously hypertensive rats. Hypertension 11:573–578

    PubMed  Google Scholar 

  40. Lüscher TF (1988) Endothelial vasoactive substances and cardiovascular disease. S Karger Publisher AG, Basel, pp 1–133

    Google Scholar 

  41. Lüscher TF, Vanhoutte PM (1988) Mechanisms of altered endothelium-dependent responses in hypertensive blood vessels. in: Vanhoutte PM (ed) Relaxing and contracting factors, biological and clinical research. Humana Press, Clifton, NJ, pp 495–509

    Chapter  Google Scholar 

  42. Lüscher TF (1989) Endothelium-derived relaxing and contracting factors: potential role in coronary artery disease. Eur Heart J 10:847–857

    PubMed  Google Scholar 

  43. Lüscher TF (1989) Imbalance of endothelium-derived relaxing and contracting factors: a new concept in hypertension? Am J Hypertension 3:317–330

    Google Scholar 

  44. Lüscher TF, Aarhus LL, Vanhoutte PM (1990) Indomethacin enhances the impaired endothelium-dependent relaxations in small mesenteric arteries of the SHR. Am J Hypertension 3:55–58

    Google Scholar 

  45. Lüscher TF, Vanhoutte PM (1990) The endothelium: modulator of cardiovascular function. CRC Press, Florida, USA, pp 1–215

    Google Scholar 

  46. Mayhan WG, Faraci FM, Heistad DD (1987) Impairment of endothelium-dependent in responses of cerebral arterioles in chronic hypertension. Am J Physiol 253:H1435–H1440

    PubMed  CAS  Google Scholar 

  47. Mayhan WG, Faraci FM, Heistad DD (1988) Responses of cerebral arterioles to adenosine diphosphate, serotonin and the thromboxane analogue U-46619 during chronic hypertension. Hypertension 12:556–561

    PubMed  CAS  Google Scholar 

  48. Miller MJS, Pinto A, Mullane KM (1987) Impaired endothelium-dependent relaxations in rabbits subjected to aortic coarctation hypertension. Hypertension 10:164–170

    PubMed  CAS  Google Scholar 

  49. Miyauchi T, Ishikawa T, Tomobe Y, Yanagisawa M, Kimura S, Sugishita Y, Ito I, Goto K, Masaki T (1989) Characteristics of pressor response to endothelin in spontaneously hypertensive Wistar-Kyoto rats. Hypertension 14:427–434

    PubMed  CAS  Google Scholar 

  50. Miyauchi T, Yanagisawa M, Suzuki N, Iida K, Sugishita Y, Fujino M, Saito T, Goto K, Masaki T (1989) Venous plasma concentrations of endothelin in normal and hypertensive subjects. Circulation 80 (Suppl II):2280–0

    Google Scholar 

  51. Moritoki H, Hosoki E, Ishida Y (1986) Age-related decrease in endothelium-dependent dilator response to histamine in rat mesenteric artery. Eur J Pharmacol 126:61–67

    Article  PubMed  CAS  Google Scholar 

  52. Nara Y, Kihara M, Mano M, Horie R, Yamori Y (1984) Dietary effect on platelet aggregation in men with and without a family history of essential hypertension. Hypertension 6:339–343

    PubMed  CAS  Google Scholar 

  53. Palmer RMJ, Ashton DS, Moncada S (1988) Vascular endothelial cells synthesize nitric oxide from L-arginine. Nature 333:664–666

    Article  PubMed  CAS  Google Scholar 

  54. Panza JA, Quyyumi AA, Epstein SE (1988) Impaired endothelium-dependent vascular relaxation in hypertensive patients (abstract). Circulation 78 (Suppl II):473–0

    Article  Google Scholar 

  55. Rees DD, Palmer RMJ, Moncada S (1989) The role of endothelium-derived nitric oxide in the regulation of blood pressure. Proc Natl Acad Sci USA 86:3375–3378

    Article  PubMed  CAS  Google Scholar 

  56. Rees DD, Palmer RMJ, Hodson HF, Moncada S (1989) A specific inhibitor of nitric oxide formation from L-arginine attenuates endothelium-dependent relaxation. Br J Pharmacol 96:418–424

    PubMed  CAS  Google Scholar 

  57. Richard V, Tanner FC, Tschudi M, Lüscher TF (1990) Differential activation of the endothelial L-arginine pathway by bradykinin, serotonin and clonidine in porcine coronary arteries. Am J Physiol 259:H1433–H1439

    PubMed  CAS  Google Scholar 

  58. Rinaldi G, Bohr D (1989) Endothelium-mediated spontaneous response in aortic rings of deoxycorticosterone acetate-hypertensive rats. Hypertension 13:256–261

    PubMed  CAS  Google Scholar 

  59. Saito Y, Nakao K, Shirakami M, Jougasaki M, Yamada T, Itoh H, Mukoyama M, Arai H, Hosoda K, Suga S, Ogawa Y, Imura H (1989) Detection and characterization of endothelin-1-like immunoreactivity in rat plasma. Biochem Biophys Res Commun 163:1512–1516

    Article  PubMed  CAS  Google Scholar 

  60. Savitsky JP, Doczi J, Black J, Arnold JD (1978) A clinical safety trial of stroma-free hemoglobin. Clin Pharmacol Ther 23:73–80

    PubMed  CAS  Google Scholar 

  61. Schini V, Hendrickson H, Heublein D, Burnett Jr J, Vanhoutte PM (1989) Thrombin enhances the release of endothelin from cultured porcine aortic endothelial cells. Eur J Pharmacol 165:333–334

    Article  PubMed  CAS  Google Scholar 

  62. Shichiri M, Hirata Y, Anao K, Emori T, Ohta K, Kimoro S, Inoue A, Marumo F (1989) Plasma endothelin levels in patients with hypertension and end-stage renal failure. Circulation 80 (Suppl II):0502–0

    Google Scholar 

  63. Shichiri M, Hirata Y, Ando K, Emori T, Ohta K, Kimoto S, Ogura M, Inoue A, Marumo F (1990) Plasma endothelin levels in hypertension and chronic renal failure. Hypertension 15:493–496

    PubMed  CAS  Google Scholar 

  64. Sim MK, Singh M (1987) Decreased responsiveness of the aortae of hypertensive rats to acetylcholine, histamine and noradrenaline. Br J Pharmacol 90:147–150

    PubMed  CAS  Google Scholar 

  65. Soltis EE (1987) Effect of age blood pressure and membrane-dependent vascular responses in the rat. Circ Res 61:889–897

    PubMed  CAS  Google Scholar 

  66. Stewart DJ, Cernacek P (1989) Plasma endothelin levels are markedly elevated in cardiogenic shock. Circulation 80 (Suppl II):2329–0

    Google Scholar 

  67. Suzuki N, Miyauchi T, Tomobe Y, Matsumoto H, Goto K, Masaki T, Fujino M (1990) Plasma concentrations of endothelin-1 in spontaneously hypertensive rats and DOCA-salt hypertensive rats. Biochem Biophys Res Commun 167:941–947

    Article  PubMed  CAS  Google Scholar 

  68. Tanner FC, Noll G, Boulanger C, Lüscher TF (1991) Oxidized low density lipoproteins inhibit relaxations of porcine coronary arteries: role of scavenger receptor and endothelium-derived nitric oxide. Circulation (in press)

    Google Scholar 

  69. Tesfamariam B, Halpern W (1988) Endothelium-dependent and endothelium-independent vasodilation in resistance arteries from hypertensive rats. Hypertension 11:440–444

    PubMed  CAS  Google Scholar 

  70. Tolins JP, Palmer RMJ, Moncada S, Raij L (1990) Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses. Am J Physiol 258:H655–H662

    PubMed  CAS  Google Scholar 

  71. Tomobe Y, Miyauchi T, Saito A, Yanagisawa M, Kimura S, Goto K, Masaki T (1988) Effects of endothelin on the renal artery from spontaneously hypertensive and Wistar Kyoto rats. Eur J Pharmacol 152:373–374

    Article  PubMed  CAS  Google Scholar 

  72. Vallance P, Collier J, Moncada S (1989) Effects of endothelium-derived nitric oxide on peripheral arteriolar tone in man. Lancet 997-1000

    Google Scholar 

  73. Valtier D, Guicheney P, Badouin-Legros M, Meyer P (1986) Platelets in human essential hypertension: in vitro hyperreactivity to thrombin. J Hypertension 4:551–555

    Article  CAS  Google Scholar 

  74. Van de Voorde J, Cuvelier C, Leusen I (1984) Endothelium-dependent relaxation effects in aorta from hypertensive rats. Arch Int Physiol Biochem 92:10–11

    Article  Google Scholar 

  75. Van de Voorde J, Leusen I (1984) Endothelium-dependent and independent relaxation effects on aorta preparations of renal hypertensive rats. Arch Int Physiol Biochem 92:35–36

    Article  Google Scholar 

  76. Van de Voorde J, Leusen I (1986) Endothelium-dependent and independent relaxation of aortic rings from hypertensive rats. Am J Physiol 250:H711–H717

    PubMed  Google Scholar 

  77. Watt PAC, Thurston H (1989) Endothelium-dependent relaxation in resistance vessels from the spontaneously hypertensive rats. J Hypertension 7:661–666

    Article  CAS  Google Scholar 

  78. Winquist RJ, Bunting PB, Baskin EP, Wallace AA (1984) Decreased endothelium-dependent relaxation in New Zealand genetic hypertensive rats. J Hypertension 2:536–541

    Article  Google Scholar 

  79. Webb RC, Vander AJ, Henry JP (1987) Increased vasodilator responses to acetylcholine in psychosocial hypertensive mice. Hypertension 9:268–276

    PubMed  CAS  Google Scholar 

  80. Wright CE, Angus JA (1986) Effects of hypertension and hypercholesteremia on vasodilatation in the rabbit. Hypertension 8:361–371

    PubMed  CAS  Google Scholar 

  81. Yanagisawa M, Kurihara H, Kimura S, Mitsui Y, Kobayashi M, Watanabe TX, Masaki T (1988) A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature 332:411–415

    Article  PubMed  CAS  Google Scholar 

  82. Ylä-Herttuala S, Palinski W, Rosenfeld ME, Parthasarathy S, Carew TE, Butler S, Witztum JL, Steinberg D (1989) Evidence for the presence of oxidatively modified low density lipoprotein in atherosclerotic lesions of rabbit and man. J Clin Invest 84:1086–1095

    Article  PubMed  Google Scholar 

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© 1991 Dr. Dietrich Steinkopff Verlag GmbH & Co. KG, Darmstadt

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Lüscher, T.F., Dohi, Y., Tanner, F.C., Boulanger, C. (1991). Endothelium-dependent control of vascular tone: effects of age, hypertension and lipids. In: Drexler, H., Zeiher, A.M., Bassenge, E., Just, H. (eds) Endothelial Mechanisms of Vasomotor Control. Steinkopff. https://doi.org/10.1007/978-3-642-72461-9_15

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