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Endothelins

A Potential Target for Pharmacological Intervention in Diseases of the Elderly

  • Review Article
  • Clinical Pharmacology
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Summary

The existence of vasoconstrictive factors originating from the endothelium was confirmed by the description of endothelin, a 21-amino-acid peptide derived from a series of precursors, preproendothelin and a 38-amino-acid big endothelin. Three isoforms of endothelin, endothelin-1, -2 and -3, and 3 receptors (ETA, ETB and ETC) have been described and cloned.

The cellular mode of action of endothelin seems to involve the modulation of intracellular calcium (through inositol trisphosphate, diacylglycerol and phospholipase C) and activation of calcium channels.

The effects of endothelin are predominantly on the cardiovascular system. Its major effect is vasoconstriction, both systemic and pulmonary, with additional positive chronotropic and inotropic effects on the heart. It has also been implicated in homeostatic regulation of kidney microcirculation, and has powerful mitogenic effects on fibroblasts and smooth muscle cells. Many additional effects have been described on the endocrine system and on other systems. However, the clinical relevance of such effects is uncertain.

Increased plasma endothelin levels have been reported in many diseases, but as yet it is not certain whether they are a cause or a consequence of the pathology. Pathologies most probably related to endothelin dysfunction are the vasospastic diseases, especially vasospasm after subarachnoid haemorrhage. Endothelin could be implicated to a lesser measure in diseases typical of the elderly population, such as hypertension or atherosclerosis.

Drugs are being developed which act on endothelin metabolism, the most promising of which appear to be the inhibitors of endothelin converting enzyme and endothelin receptor antagonists. Some already existing drugs, such as calcium channel blockers or angiotensin converting enzyme inhibitors, probably act at least in part by interfering with endothelin metabolism or effects.

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References

  • Abassi ZA, Tate JE, Golomb E, et al. Role of NEP in the metabolism of endothelin. Hypertension 20: 89–95, 1992

    PubMed  CAS  Google Scholar 

  • Allen SW, Chatfield BA, Koppenhafer SA, et al. Circulating immunoreactive endothelin-1 in children with pulmonary hypertension. American Review of Respiratory Disease 148: 519–522, 1993

    PubMed  CAS  Google Scholar 

  • Andrawis NS, Gilligan J, Abernethy DR. Endothelin-1 mediated vasoconstriction: specific blockade by verapamil. Clinical Pharmacology and Therapeutics 52: 583–589, 1992

    PubMed  CAS  Google Scholar 

  • Arai H, Hori S, Aramori I, et al. Cloning an expression of a cDNA encoding an endothelin receptor. Nature 348: 730–732, 1990

    PubMed  CAS  Google Scholar 

  • Arendt RM, Wilbert-Lamper U, Heucke L. Increased plasma endothelin in patients with hyperlipoproteinemia and stable and unstable angina. Abstract. Circulation 82(Suppl. III): III248, 1990

    Google Scholar 

  • Arinami T, Ishikawa M, Inoue A, et al. Chromosomal assignments of the human endothelin family genes: the endothelin-1 gene (EDN1) to 6p-3p24, the endothelin-2 gene (EDN2) to 1p34, and the endothelin 3 gene (EDN3) to 20q13.2-q13.3. American Journal of Human Genetics 48: 990–996, 1991

    PubMed  CAS  Google Scholar 

  • Asano T, Ikegaki I, Suzuki Y, et al. Endothelin and the production of cerebral vasospasm in dogs. Biochemical and Biophysical Research Communications 159: 1345–1351, 1990

    Google Scholar 

  • Badr KF, Murray JJ, Breyer MD, et al. Mesangial cell, glomerular and renal vascular responses to endothelin in the rat kidney. Journal of Clinical Investigation 83: 336–342, 1989

    PubMed  CAS  Google Scholar 

  • Battistini B, d’Orleans-Juste P, Sirois P. Endothelins: circulating plasma levels and presence in other biologic fluids. Laboratory Investigation 68: 600–628, 1993

    PubMed  CAS  Google Scholar 

  • Battistini B, Filep J, Sirois P. Potent thromboxane-mediated in vitro bronchoconstrictor effect of endothelin in the guinea-pig. European Journal of Pharmacology 165: 215–222, 1990

    Google Scholar 

  • Bloch KD, Eddy RL, Shows TB, et al. cDNA cloning and chromosomal assignment of the gene encoding endothelin-3. Journal of Biological Chemistry 264: 18156–18161, 1989

    PubMed  CAS  Google Scholar 

  • Bloch KD, Freidrich SP, Lee ME, et al. Structural organization and chromosomal assignment of the gene encoding endothelin. Journal of Biological Chemistry 264: 10851–10857, 1989

    PubMed  CAS  Google Scholar 

  • Bonvallet ST, Oka M, Yano M, Zamora MR, McMurthy IF. BQ123, and ETA receptor antagonist, attenuates endothelin-1 induced vasoconstriction in rat pulmonary circulation. Journal of Cardiovascular Pharmacology 22: 39–43, 1993

    PubMed  CAS  Google Scholar 

  • Boulanger C, Lüscher TF. Release of endothelin from the porcine aorta; inhibition by endothelium-derived nitric oxide. Journal of Clinical Investigation 85: 587–590, 1990

    PubMed  CAS  Google Scholar 

  • Boulanger CM, Tanner FC, Bea M, et al. Oxidized low-density lipoproteins induce mRNA expression and release of endothelin from the human and porcine endothelium. Circulation Research 70: 1191–1197, 1992

    PubMed  CAS  Google Scholar 

  • Braquet P, Touvay C, Lagente V, et al. Effect of endothelin-1 on blood pressure and bronchopulmonary system of the guinea pig. Journal of Cardiovascular Pharmacology 13(Suppl.5): S143–S145, 1989

    PubMed  CAS  Google Scholar 

  • Breu B, Löffler BM, Clozel M. In vitro characterization of Ro 46-2005, a novel synthetic non-peptide endothelin antagonist of ETA and ETB receptors. Febs Letters 334: 210–214, 1993

    PubMed  CAS  Google Scholar 

  • Brown MR, Vanghan J, Jimenez LL, et al. Transforming growth factor-13: role in mediating serum-induced endothelin production by vascular endothelial cells. Endocrinology 129: 2355–2360, 1991

    PubMed  CAS  Google Scholar 

  • Bunker CB, Terenghi G, Springall DR, et al. Deficiency of calcitonin gene related peptide in Raynaud’s phenomenom. Lancet 336: 1530–1533, 1990

    PubMed  CAS  Google Scholar 

  • Cacoub P, Dorent R, Maistre G, et al. Endothelin-1 in primary pulmonary hypertension and the Eisenmenger syndrome. American Journal of Medicine 71: 448–450, 1993

    CAS  Google Scholar 

  • Calvo IJ, Gonzales R, de Carvalho LF, et al. Release of substance P from rat hypothalamus and pituitary by endothelin. Endocrinology 126: 2288–2295, 1990

    PubMed  CAS  Google Scholar 

  • Cernacek P, Stewart DJ. Immunoreactive endothelin in human plasma: marked elevations in patients with cardiogenic shock. Biochemical and Biophysical Research Communications 161: 562–567, 1989

    PubMed  CAS  Google Scholar 

  • Cimminiello C, Milani M, Uberti T, et al. Endothelin, vasoconstriction, and endothelial damage in Raynaud’s phenomenom. Lancet 337: 114–115, 1991

    PubMed  CAS  Google Scholar 

  • Clozel M, Breu V, Burri K, Cassai JM, Fischli W, et al. Pathophysiological role of endothelin revealed by the first orally active endothelin receptor antagonist. Nature 365: 759–761, 1993

    PubMed  CAS  Google Scholar 

  • Cody RJ, Haas GJ, Binkley PL, et al. Plasma endothelin correlates with the extent of pulmonary hypertension in patients with chronic heart failure. Circulation 85: 504–509, 1992

    PubMed  CAS  Google Scholar 

  • Collier A, Leach JP, McLellan A, et al. Plasma endothelin-like immunoreactivity levels in IDDM patients with microalbuminuria. Diabetes Care 15: 1038–1040, 1992

    PubMed  CAS  Google Scholar 

  • Collier J, Vallance P. Physiological importance of nitric oxide. An endogenous vasodilatator. British Medical Journal 302: 1289–1290, 1991

    PubMed  CAS  Google Scholar 

  • Cozza EN, Chiou S, Gomez-Sanchez CE. Endothelin-1 potentialisation of angiotensin II stimulation of aldosterone production. American Journal of Physiology 262: R85–R89, 1992

    PubMed  CAS  Google Scholar 

  • de Nucci G, Thomas R, d’Orleansuste Antunes E, et al. Pressor effects of circulating endothelin are limited by its removal in the pulmonary circulation and by the release of prostacyclin and endothelium-derived relaxing factor. Proceedings of the National Academy of Sciences of the USA 85: 9797–9800, 1988

    PubMed  Google Scholar 

  • Emori M, Hirata Y, Ohta K, et al. Cellular mechanisms of endothelin-1 release by angiotensin and vasopressin. Hypertension 18: 165–170, 1991

    PubMed  CAS  Google Scholar 

  • Emori T, Hirata Y, Marumo F. Specific receptors for endothelin-3 in cultured bovine endothelial cells and its cellular mechanism of action. Febs Letters 263: 261–264, 1990

    PubMed  CAS  Google Scholar 

  • Ezra D, Goldstein RE, Czaja JF, et al. Lethal ischemia due to intracoronary endothelin in pigs. American Journal of Physiology 257: 339–343, 1989

    Google Scholar 

  • Fukuroda T, Noguchi K, Tsuchida S, et al. Inhibition of biological actions of big endothelin-1 by phosphoramidon. Biochemical and Biophysical Research Communications 172: 390–395, 1990

    PubMed  CAS  Google Scholar 

  • Furchgott RF, Zawadzki JV. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 286: 373–376, 1980

    Google Scholar 

  • Fyhrquist F, Sirviö ML, Helin K, Saijonmaa O, Metsärinne K, et al. Endothelin antiserum decreases volume-stimulated and basal plasma concentration of atrial natriuretic peptide. Circulation 88: 1172–1176, 1993

    PubMed  CAS  Google Scholar 

  • Goetz KL, Mang B, Madwed JB, et al. Cardiovascular, renal and endocrine responses to intravenous endothelin in conscious dogs. American Journal of Physiology 155: R1064–R1068, 1988

    Google Scholar 

  • Goto K, Kasuya K, Matsuki N, et al. Endothelin activates the dihydropyridine-sensitive, voltage-dependant Ca 2+ channel in vascular smooth muscle cells. Proceedings of the National Academy of Sciences of the USA 86: 3915–3918, 1989

    PubMed  CAS  Google Scholar 

  • Gugiura M, Inagami T, Kon V. Endotoxin stimulates endothelin release in vivo and in vitro as determined by radioimmunoassay. Biochemical and Biophysical Research Communications 161: 1220–1227, 1989

    Google Scholar 

  • Habuchi Y, Tanaka H, Furukawa T, et al. Endothelin enhances delayed potassium current via phospholipase C in guinea pig ventricular myocytes. American Journal of Physiology 262: F799–F806, 1992

    Google Scholar 

  • Hirata Y, Fukuda Y, Marumo F. Endothelin is a potent mitogen for rat vascular smooth muscle cells. Atherosclerosis 78: 225–228, 1989

    PubMed  CAS  Google Scholar 

  • Hiroe M, Hirata Y, Fujita N, et al. Plasma endothelin-1 levels in idiopathic dilated cardiomyopathy. American Journal of Cardiology 68: 1114–1115, 1991

    PubMed  CAS  Google Scholar 

  • Hori S, Komatsu Y, Shigemoto R, et al. Distinct tissue distribution and cellular localization of two messenger ribonucleic acids encoding different subtypes of rat endothelin receptors. Endocrinology 130: 1885–1895, 1992

    PubMed  CAS  Google Scholar 

  • Horio T, Kohno M, Murakawa K, et al. Increased plasma immunoreactive endothelin-1 concentration in hypercholesterolemic rats. Atherosclerosis 89: 239–246, 1991

    PubMed  CAS  Google Scholar 

  • Hu RM, Levin ER, Pedram A, et al. Atrial natriuretic peptide inhibits the production and the secretion of endothelium from cultured endothelial cells. Journal of Biological Chemistry 267: 17384–17389, 1992

    PubMed  CAS  Google Scholar 

  • Ihara M, Fukuroda T, Saeki T, et al. An endothelin receptor (ETA) antagonist isolated from Streptomyces misakiensis. Biochemical and Biophysical Research Communications 178: 132–137, 1991

    PubMed  CAS  Google Scholar 

  • Ihara M, Noguchi K, Saeki T, et al. Biological profiles of highly potent novel potent endothelin antagonists selective for ETA receptor. Life Sciences 50: 247–255, 1992a

    PubMed  CAS  Google Scholar 

  • Ihara M, Saeki T, Fukuroda T, et al. A novel radioligand [125I] BQ3020 selective for endothelin (ETB) receptors. Life Sciences 51: 47–52, 1992b

    Google Scholar 

  • Imai T, Hirat Y, Emori T, et al. Induction of endothelin-1 gene by angiotensin II and vasopressine in endothelial cells. Hypertension 19: 181–188, 1992

    Google Scholar 

  • Inoue A, Yanagisawa M, Kimura S, et al. The human endothelins family: three structurally and pharmacologically distinct isopeptides predicted by three separate genes. Proceedings of the National Academy of Sciences of the USA 86: 2863–2867, 1989

    PubMed  CAS  Google Scholar 

  • Inoue Y, Yanagisawa M, Takuwa Y, et al. The human prepro-endothelin-1 gene. Journal of Biological Chemistry 264: 14954–14959, 1990

    Google Scholar 

  • Ishikawa T, Yanagisawa M, Kimura S, et al. Positive inotropic action of novel vasoconstrictor peptide endothelin on guinea pig atria. American Journal of Physiology 155; H970–973, 1988

    Google Scholar 

  • Itoh S, Sasaki T, Ide K, Ishikawa K, Nishikibe M, et al. A novel endothelin ETA receptor antagonist, BQ-485, and its preventive effect on experimental cerebral vasospasm in dogs. Biochemical and Biophysical Research Communications 195: 969–975, 1993

    PubMed  CAS  Google Scholar 

  • Itoh Y, Yanagisawa M, Ohkubo S, et al. Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. Febs Letters 231: 440–444, 1988

    PubMed  CAS  Google Scholar 

  • Kanno K, Hirta Y, Shichiri M, et al. Plasma endothelin-1 levels in patients with diabetes mellitus with or without vascular complication. Journal of Cardiovascular Pharmacology 17: S475–S476, 1991

    PubMed  Google Scholar 

  • Kanse SM, Takahashi K, Warren JB, et al. Glucocorticoids induce endothelin release from vascular smooth muscle cells but not endothelial cells. European Journal of Pharmacology 199: 99–101, 1991

    PubMed  CAS  Google Scholar 

  • Kanyicska B, Burris TP, Freeman ME. The effects of endothelins on secretion of prolactin, luteinizing hormone and follicle-stimulating hormone are mediated by different guanine nucleotide-binding proteins. Endocrinology 129: 2607–2613, 1992

    Google Scholar 

  • Karne S, Jayawickreme CK, Lerner MR. Cloning and characterization or an endothelin-3 specific receptor (ETc receptor) from Xenopus laevis dermal melanophores. Journal of Biological Chemistry 268: 19126–19133, 1993

    PubMed  CAS  Google Scholar 

  • Katoh K, Mizuno K, Sanada H, et al. Effect of aging on endothelin induced prostaglandin 12 release in isolated hind legs of the spontaneously hypertensive rats. Research Communications in Chemical Pathology and Pharmacology 74: 185–199, 1991

    PubMed  CAS  Google Scholar 

  • Kawamura M, Naruse K, Ohgawara H, et al. Increased plasma endothelin in NIDDM patients with retinopathy. Diabetes Care 15: 1396–1398, 1992

    PubMed  CAS  Google Scholar 

  • Khono M, Yokokawa K, Horio T, et al. Atrial and brain natriuretic peptides inhibit the endothelin-1 secretory response to angiotensin-II in porcine aorta. Circulation Research 70: 241–247, 1992

    Google Scholar 

  • Kioswki W, Linder L. Reversal of endothelin-1 induced vasoconstriction by nifedipine in human resistance vessels in vivo in healthy subjects. American Journal of Cardiology 69: 1063–1066, 1992

    Google Scholar 

  • Kiubo SH, Rector TS, Bank AJ, et al. Endothelium-dependent vasodilatation in patients with heart failure. Circulation 84: 1589–1596, 1991

    Google Scholar 

  • Kloog Y, Ambar I, Sokolowsky M, et al. Sarafotoxin, a novel vasoconstrictor peptide: phosphoinositide hydrolysis in rat heart and brain. Science 242: 268–270, 1988

    PubMed  CAS  Google Scholar 

  • Kloog Y, Sokolovsky M. Similarities in mode and sites of action of sarafotoxins and endothelins. Trends in Pharmacological Sciences 10: 212–214, 1989

    PubMed  CAS  Google Scholar 

  • Koller A, Kaley G. Endothelial regulation of wall shear stress and blood flow in skeletal muscle microcirculation. American Journal of Physiology 260: H862–H868, 1991

    PubMed  CAS  Google Scholar 

  • Kon V, Yoshioka T, Fogo A, et al. Glomerular actions of endothelin in vivo. Journal of Clinical Investigation 83: 708–712, 1989

    Google Scholar 

  • Koseki C, Imai M, Hirata Y, et al. Autoradiographic distribution in rat tissues of binding-sites for endothelin: a neuropeptide? American Journal of Physiology 256: R858–R866, 1989

    PubMed  CAS  Google Scholar 

  • Kourembanas S, Marsden PA, McQuillan LP, et al. Hypoxia induces endothelin gene expression and secretion in cultured human endothelium. Journal of Clinical Investigation 88: 1054–1057, 1991

    PubMed  CAS  Google Scholar 

  • Koyama H, Tabata T, Nishazawa Y, et al. Plasma endothelin levels in patients with uraemia. Lancet 1: 991–992, 1989

    PubMed  CAS  Google Scholar 

  • Kureya P, Beevers DG. The mechanisms of hypertension and the role of ACE inhibitors. Journal of Human Hypertension 5(Suppl. 2): 3–8, 1991

    PubMed  Google Scholar 

  • Kurihara H, Yamaoki K, Nagai R, et al. Endothelin: a potent vasoconstrictor associated with coronary vasospasm. Life Sciences 44: 1937–1943, 1989

    PubMed  CAS  Google Scholar 

  • Kurihara H, Yoshizumi M, Sugiyama T, et al. Transforming growth factor B stimulates the expression of endothelin mRNA by vascular endothelial cells. Biochemical and Biophysical Research Communications 159: 1435–1440, 1989

    PubMed  CAS  Google Scholar 

  • Lanese DM, Conger JD. Effects of endothelin receptor antagonist on cyclosporin-induced vasoconstriction in isolated rat renal arterioles. Journal of Clinical Investigation 91: 2144–02149, 1993

    PubMed  CAS  Google Scholar 

  • Lemonnier de Gouville A, Lippton H, Cohen G, et al. Vasodilatator activity of endothelin-1 and endothelin-3: rapid development of crosstachyphylaxis and dependance on the rate of endothelin administration. Journal of Pharmacology and Experimental Therapeutics 254: 1024–1028, 1990

    CAS  Google Scholar 

  • Lerman A, Edwards BS, Hallett JW, et al. Circulating and tissue endothelin immunoreactivity in advanced atherosclerosis. New England Journal of Medicine 325: 997–1001, 1991

    PubMed  CAS  Google Scholar 

  • Lerman A, Webster MWI, Chesebro JH, Edwards WD, Wei CM, et al. Circulating and tissue endothelin immunoreactivity in hypercholesterolaemic pigs. Circulation 88: 2923–2928, 1993

    PubMed  CAS  Google Scholar 

  • Lévesque H, Delpelch B, Chauzy C, et al. Effects of endothelin on hyaluronan production by human fetal fibroblasts in culture, International Journal of Microcirculation — Clinical and Experimental 2(Suppl. 1):S25, 1992

    Google Scholar 

  • Lévesque H, Moore N, Thuillez C, et al. Les endothelines: une nouvelle classe de peptides vasoactifs. Therapie 47: 53–56, 1992

    PubMed  Google Scholar 

  • Lévesque H, Sevrain L, Freger P, et al. Raised plasma endothelin in aneurysmal subarachnoid haemorrhage. Lancet 1: 290, 1990

    Google Scholar 

  • Lin HY, Kaji EH, Winkel GK, et al. Cloning and functional expression of a vascular smooth muscle endothelin-1 receptor. Proceedings of the National Academy of Sciences of the USA 88: 3185–3189, 1991

    PubMed  CAS  Google Scholar 

  • Lindblad LE, Ekenvall L, Etzell BM, et al. Adrenoreceptors in Raynaud’s disease. Journal of Cardiovascular Pharmacology 14: 881–885, 1989

    PubMed  CAS  Google Scholar 

  • Liu Y, Geisbuhler B, Jones AW. Activation of multiple mechanisms including phospholipase D by endothelin-1 in rat aorta. American Journal of Physiology 262: C941–C949, 1992

    PubMed  CAS  Google Scholar 

  • Lüscher TF, Bock AH, Yang Z, et al. Endothelium-derived relaxing and contracting factors: perspectives in nephrology. Kidney International 39: 575–590, 1991

    PubMed  Google Scholar 

  • Lüscher TF, Boulanger CM, Yang Z, et al. Interactions between endothelium-derived relaxing and contracting factors in health and cardiovascular disease. Circulation 87(Suppl V): 36–44, 1993a

    Google Scholar 

  • Lüscher TF, Haefeli WE. L-arginine in the clinical arena: tool or remedy? Editorial. Circulation 87: 1746–1749, 1993

    PubMed  Google Scholar 

  • Lüscher TF, Oemar BS, Boulanger CM, et al. Molecular and cellular biology of endothelin and its receptors. Journal of Hypertension 11: 7–11, 121-126, 1993b

    PubMed  Google Scholar 

  • Lüscher TF, Tanner TC, Dohi Y. Age, hypertension and hypercholesterolaemia alter endothelium-dependent vascular regulation. Pharmacology and Toxicology 70(Suppl.2): S32–S39, 1992

    PubMed  Google Scholar 

  • Masaki T. Endothelins: homeostatic and compensatory actions in the circulatory and endocrine sytems. Endocrine Reviews 14: 256–258, 1993

    PubMed  CAS  Google Scholar 

  • Masaki T. Overview: reduced sensitivity of vascular response to endothelin. Circulation 87(Suppl.5): V33–V35, 1993

    CAS  Google Scholar 

  • Masaki T, Yanagisawa M, Goto K. Physiology and pharmacology of endothelins. Medicinal Research Reviews 12: 391–421, 1992

    PubMed  CAS  Google Scholar 

  • Masoaka H, Suzuki R, Hirata Y, et al. Raised plasma endothelin in subarachnoid haemorrhage. Lancet 2: 1402, 1990

    Google Scholar 

  • Matsumura Y, Hisaki K, Takaota M, et al. Phosphoramidon, a metalloproteinase inhibitor, suppresses the hypertensive effects of big endothelin-1. European Journal of Pharmacology 185: 103–106, 1990

    PubMed  CAS  Google Scholar 

  • McKay KO, Black JL, Armour CL. The mechanisms of action of endothelin in human lungs. British Journal of Pharmacology 102: 422–428, 1991

    PubMed  CAS  Google Scholar 

  • McMahon EG, Palomo M, Moore WM, et al. Phosphoramidon blocks the pressor activity of porcine big endothelin-1 in vivo and conversion of big endothelin-1 to endothelin-1. Proceedings of the National Academy of Sciences of the USA 88: 703–707, 1991

    PubMed  CAS  Google Scholar 

  • Miller WL, Redfield MM, Burnett JC. Integrated cardiac renal and endocrine actions of endothelin. Journal of Clinical Investigation 83: 317–320, 1989

    PubMed  CAS  Google Scholar 

  • Miyauchi T, Suzuki N, Kurihara T, et al. Endothelin-1 and endothelin-3 play different roles in acute and chronic alterations of blood pressure in patients with chronic hemodialysis. Biochemical and Biophysical Research Communications 178: 276–281, 1991

    PubMed  CAS  Google Scholar 

  • Miyauchi T, Yanagisawa M, Iida K, et al. Age and sex-related variation of plasma endothelin-1 concentration in normal and hypertensive patients. American Heart Journal 123: 1092–1093, 1992

    PubMed  CAS  Google Scholar 

  • Moncada S, Gryglewski R, Bunting S, et al. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature 263: 663–665, 1976

    PubMed  CAS  Google Scholar 

  • Moravec S-C, Reynols EE, Stewart RW, et al. Endothelin is a positive inotropic agent in human and rat heart. Biochemical and Biophysical Research Communications 159: 14–18, 1989

    PubMed  CAS  Google Scholar 

  • Mortensen LH, Fink JD. Captopril prevents chronic hypertension produced by infusion of endothelin-1 in rats. Hypertension 19: 676–680, 1992

    PubMed  CAS  Google Scholar 

  • Mozes T, Zijlstra FJ, Heiligers JPC, et al. Sequential release of tumor necrosis factor, platelet activiting factor and eicosanoids during endotoxin shock in anaesthetized pigs; protective effects of indomethacin. British Journal of Pharmacology 88: 1054–1057, 1991

    Google Scholar 

  • Nakamichi K, Ihara M, Kobayashi M, et al. Different distribution of endothelin receptor subtypes in pulmonary tissue revealed by the novel selective ligands BQ-123 and [Ala1,3,11,15] ET-1. Biochemical and Biophysical Research Communications 182: 144–150, 1992

    PubMed  CAS  Google Scholar 

  • Nakamura T, Kasai K, Sekiguchi Y, et al. Elevation of plasma endothelin concentrations during endotoxic shock in dogs. European Journal of Pharmacology 205: 277–282, 1991

    PubMed  CAS  Google Scholar 

  • Naruse M, Kaana M, Hifumi S, et al. Plasma immunoreactive endothelin but not thrombomodulin is increased in essential hypertension and ischemic heart diseases. Journal of Cardiovascular Pharmacology 17: S471–S474, 1991

    PubMed  Google Scholar 

  • Naruse K, Naruse M, Watanabe Y, et al. Molecular form of immunoreactive endothelin in plasma and urine of normal patients with various diseases states. Journal of Cardiovascular Pharmacology 17: S506–S508, 1991

    PubMed  Google Scholar 

  • Natsumura Y, Ykegawa R, Suzuki Y, et al. Phosphoramidon prevents cerebral vasospasm following subarachnoid haemorrhage in dogs: the relationship to endothelin-1 levels in the cerebrospinal fluid. Life Sciences 49: 841–848, 1991

    Google Scholar 

  • Nayler WG. The molecular basis for use of calcium antagonists in ischaemic heart disease. Drugs 43(Suppl. 1): 21–27, 1992

    PubMed  Google Scholar 

  • Numez DJR, Brown MJ, Davenport AP, et al. Endothelin-1 mRNA is widely expressed in porcine and human tissues. Journal of Clinical Investigation 85: 1537–1541, 1990

    Google Scholar 

  • O’Brien R, Robbins RJ, McMurthy IF. Endothelial cells in culture produce a vasoconstrictive substance. Journal of Cell Physiology 135: 263–270, 1987

    Google Scholar 

  • Ohkubo S, Ogi K, Hosoya M, et al. Specific expression of human endothelin 2 (ET-2) gene in a renal adenocarcinoma cell line. Molecular cloning of cDNA encoding the precursor of ET-2 and its characterization. Febs Letters 274: 136–140, 1990

    PubMed  CAS  Google Scholar 

  • Okada K, Miyazaki Y, Takada J, et al. Conversion of big endothelin 1 by membrane-bound methalloendopeptidase in cultured bovine endothelial cells. Biochemical and Biophysical Research Communications 171: 1192–1198, 1990

    PubMed  CAS  Google Scholar 

  • Oliver FJ, de la Rubia G, Freener EP, et al. Stimulation of endothelin-1 gene expression by insulin in endothelial cell. Journal of Biological Chemistry 266: 23251–23256, 1991

    PubMed  CAS  Google Scholar 

  • Opgenorth TJ, Wu-Wong JR, Shiosaki K. Endothelin-converting enzymes. FASEB Journal 6: 2653–2659, 1992

    PubMed  CAS  Google Scholar 

  • Otsuka A, Mikami H, Katahira K, et al. Changes in plasma renin activity and aldosterone concentration in response to endothelin injections in dogs. Acta Endocrinologica (Copenhagen) 121: 361–364, 1989

    CAS  Google Scholar 

  • Pakuji H, Tabuchi Y, Nakamaru M, et al. Endothelin activates the vascular renin angiotensin system in rat mesenteric arteries. Biochemistry International 21: 867–872, 1990

    Google Scholar 

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

    PubMed  CAS  Google Scholar 

  • Palmer RMJ, Ferrige AG, Moncada S. Nitric oxide release accounts for the biological activity of endothelium-derived relaxing factor. Nature 327: 524–526, 1987

    PubMed  CAS  Google Scholar 

  • Pittet JF, Morel DR, Hemsen A, et al. Elevated plasma endothelin-1 concentrations are associated with the severity of illness in patients with sepsis. Annals of Surgery 213: 261–264, 1991

    PubMed  CAS  Google Scholar 

  • Plews PL, Abdel-Malek ZA, Doupnick CA, et al. Endothelin stimulates chloride secretion across canine tracheal epithelium. American Journal of Physiology 261: L188–194, 1991

    PubMed  CAS  Google Scholar 

  • Remuzzi G, Benigni A. Endothelins in the control of cardiovascular and renal function. Lancet 342: 589–593, 1993

    PubMed  CAS  Google Scholar 

  • Resink TJ, Scott-Burden T, Buhler FR. Activation of phospholipase A2 by endothelin in cultured vascular smooth muscle cells. Biochemical and Biophysical Research Communications 158: 279–286, 1989

    PubMed  CAS  Google Scholar 

  • Rosolowsky W, Cambell WB. Endothelin enhances adrenocorticotropin-stimulated aldosterone release from cultured bovine adrenal cells. Endocrinology 126: 1860–1866, 1990

    PubMed  CAS  Google Scholar 

  • Roux SP, Clozel M, Sprecher U, Gray G, Clozel JP. Ro 47-0203, a new endothelin receptor antagonist, reverses chronic vasospasm in experimental subarachnoid hemorrhage. Abstract. Circulation 88: 1.170, 1993

    Google Scholar 

  • Sakurai T, Yanagisawa M, Inoue A, et al. cDNA cloning, sequence analysis and tissue distribution of rat preproendothelin-1 mRNA. Biochemical and Biophysical Research Communications 175: 44–47, 1991

    PubMed  CAS  Google Scholar 

  • Sakurai T, Yanagisawa M, Masaki T. Molecular characterization of endothelins receptors. Trends in Pharmacological Sciences 13: 103–108, 1992

    PubMed  CAS  Google Scholar 

  • Sakurai T, Yanagisawa M, Takuwa Y, et al. Cloning of a cDNA encoding of a non-isopeptide-selective subtype of the endothelin receptor. Nature 348: 732–735, 1990

    PubMed  CAS  Google Scholar 

  • Schriffin EL, Thibault G. Plasma endothelin in human essential hypertension. American Journal of Hypertension 4: 303–308, 1991

    Google Scholar 

  • Seki T, Ihara M, Kukuroda M, et al. [Ala1,3,11,151]Endothelin-1 analogs with ETB agonistic activity. Biochemical Biophysical Research Communications 179: 286–292, 1991

    Google Scholar 

  • Shichiri M, Hirata Y, Ando K, et al. Plasma endothelin levels in hypertension and chronic renal failure. Hypertension 15: 493–496, 1990

    PubMed  CAS  Google Scholar 

  • Shigeno T, Mima T, Yanagisawa M, et al. Prevention of cerebral vasospasm by actinomycin D. Journal of Neurosurgery 74: 940–943, 1991

    PubMed  CAS  Google Scholar 

  • Shirakami G, Nakao KI, Saito Y, et al. Acute pulmonary alveolar hypoxia increases lung and plasma endothelin-1 levels in conscious rats. Life Sciences 48: 969–976, 1991

    PubMed  CAS  Google Scholar 

  • Simonson MS, Wann S, Mene P, et al. Endothelin stimulates phospholipase C, Na+/K+ exchange, c-fos expression and mitogenesis in rat mesangial cells. Journal of Clinical Investigation 83: 708–712, 1989

    PubMed  CAS  Google Scholar 

  • Smits P, Hofman H, Wollersheim H, et al. Endothelin-1 in patients with Raynaud’s phenomenon!. Lancet 337: 236, 1991

    PubMed  CAS  Google Scholar 

  • Stasch JP, Hirth-Dietrich C, Kazda S, et al. Endothelin stimulates release of atrial natriuretic peptide in vitro and in vivo. Life Sciences 45: 869–875, 1989

    PubMed  CAS  Google Scholar 

  • Stewart DJ, Cernacek P, Costello KB, et al. Elevated endothelin-1 in heart failure and loss of normal response to postural change. Circulation 85: 510–517, 1992

    PubMed  CAS  Google Scholar 

  • Stewart DJ, Levy RD, Cernacek P, et al. Increased plasma endothelin-1 in pulmonary hypertension: marker or mediator of disease. Annals of Internal Medicine 114: 464–469, 1991

    PubMed  CAS  Google Scholar 

  • Suzuki H, Masoaka H, Hirata Y, et al. The role of endothelin-1 in the origin of cerebral vasospasm in patients with aneurysmal subarachnoid haemorrhage. Journal of Neurosurgery 77: 96–100, 1992

    PubMed  CAS  Google Scholar 

  • Suzuki H, Sato S, Suzuki Y, et al. Endothelin immunoreactivity in cerebrospinal fluid of patients with subarachnoid haemorrhage. Annals of Internal Medicine 22: 233–236, 1990

    CAS  Google Scholar 

  • Takahashi K, Ghatei MA, Lam HC, et al. Elevated plasma endothelin in patients with diabetes mellitus. Diabetologia 33: 306–310, 1990

    PubMed  CAS  Google Scholar 

  • Toko-oya T, Aizawa T, Suzuki N, et al. Increased plasma level of endothelin-1 and coronary spasm induction in patients with vasospactic angina pectoris. Circulation 83: 476–483, 1991

    Google Scholar 

  • Tomita K, Ujüe K, Nakasnihi T, et al. Plasma endothelin levels in patients with acute renal failure. New England Journal of Medicine 33: 306–310, 1989

    Google Scholar 

  • Vanhoutte PM, Rubanyi GM, Miller VM, et al. Modulation of vascular smooth muscle contraction by endothelium. Annual Review of Physiology 48: 307–320, 1986

    PubMed  CAS  Google Scholar 

  • Vierhapper H, Wagner O, Nowotny P, et al. Effect of endothelin-1 in man. Circulation 81: 1415–1418, 1990

    PubMed  CAS  Google Scholar 

  • Vigne P, Ladoux A, Prelin C. Endothelin activates Na+/H+ exchange in brain capillary endothelial cells via a high affinity endothelin-3 receptor that is not coupled to phospholipase C. Journal of Biological Chemistry 266: 5925–5928, 1991

    PubMed  CAS  Google Scholar 

  • Weitzberg E, Lundberg JM, Rudehill A. Elevated plasma levels of endothelin in patients with sepsis syndrome. Circulatory Shock 33: 222–227, 1991

    PubMed  CAS  Google Scholar 

  • Whittle BJR, Moncada S. The endothelin explosion: a pathophysiological reality or a biological curiosity. Circulation 81: 2022–2025, 1990

    PubMed  CAS  Google Scholar 

  • Yakokawa K, Tahara H, Kohno M, Murakawa K, Yanusari K, et al. Hypertension associated with endothelin-secreting malignant hemangioendothelioma. Annals of Internal Medicine 114: 213–215, 1991

    Google Scholar 

  • Yamakado M, Hirata Y, Matsuoka H, et al. Pathophysiological role of endothelin in renal transplantation. Journal of Cardiovascular Pharmacology 17: S477–S479, 1991

    PubMed  Google Scholar 

  • Yanagisawa M, Kurihara H, Kimura S, et al. A novel potent vasoconstrictor peptide produced by vascular endothelial cells. Nature (London) 332: 2022–2025, 1988

    Google Scholar 

  • Yanagisawa M, Masaki T. Biochemistry and molecular biology of endothelins. Trends in Pharmacological Sciences 10: 374–378, 1989

    PubMed  CAS  Google Scholar 

  • Yano M, Okada K, Takada J, et al. Endothelin converting enzyme and its in vitro and in vivo inhibition. Journal of Cardiovascular Pharmacology 17(Suppl. 7): 29–33, 1991

    Google Scholar 

  • Yasuda M, Kohno M, Tahara A, et al. Circulating immunoreactive endothelin in ischemic heart desease. American Heart Journal 119: 801–806, 1990

    PubMed  CAS  Google Scholar 

  • Yasujima M, Abe K, Kanazawa M, et al. Antihypertensive effects of captopril and enalapril in endothelin-infused rats. Journal of Experimental Medicine 163: 219–227, 1991

    CAS  Google Scholar 

  • Yoshibayashi M, Nishioka K, Nakao K, et al. Plasma endothelin concentrations in plasma with pulmonary hypertension associated with congenital heart defects. Evidence for increased production of endothelin in pulmonary circulation. Circulation 84: 2280–2285, 1991

    PubMed  CAS  Google Scholar 

  • Yoshizawa T, Shinmi O, Giaid A, et al. Endothelin: a novel peptide in the posterior pituitary system. Science 247: 462–464, 1990

    PubMed  CAS  Google Scholar 

  • Yoshizumi M, Kurihara H, Morita T, et al. Interleukin 1 increases the production of endothelin-1 release cultured endothelial cells. Biochemical and Biophysical Research Communications 166: 324–329, 1990

    PubMed  CAS  Google Scholar 

  • Zachary I, Sinnett-Smith J, Rozengurt E. Stimulation of tyrosine kinase activity in anti-phosphotyrosine immune complex of Swiss 3T3 cell lysates occurs rapidly after addition of bombesin, vasopressin, and endothelin to intact cells. Journal of Biological Chemistry 266: 24126–24133, 1991

    PubMed  CAS  Google Scholar 

  • Zamora MR, O’Brien RF, Rutherford RB, et al. Serum endothelin-1 concentrations and cold provocation in primary Raynaud’s phenomenon!. Lancet 336: 1144–1147, 1990

    PubMed  CAS  Google Scholar 

  • Zeidel ML, Brady HR, Kone BC, et al. Endothelin, a peptide inhibitor of Na+/K+ — ATPase in intact renal tubular epithelial cells. American Journal of Physiology 257: C1101–C1107, 1989

    PubMed  CAS  Google Scholar 

  • Zeng ZP, Naruse M, Guan BJ, et al. Endothelin stimulates aldosterone secretion in vitro from normal adrenocortical tissue, but not adenoma tissue in primary aldosteronism. Journal of Clinical Endocrinology and Metabolism 74: 874–878, 1992

    PubMed  CAS  Google Scholar 

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  1. Departments of Internal Medicine and Pharmacology, and VACOMED Group Research, Centre Hospitalier Universitaire Rouen-Boisguillaume, Rouen Cedex, France

    Hervé Lévesque, Nicholas Moore, Nicole Cailleux, Vincent Richard, Christian Thuillez & Hubert Courtois

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  1. Hervé Lévesque
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Lévesque, H., Moore, N., Cailleux, N. et al. Endothelins. Drugs & Aging 4, 221–237 (1994). https://doi.org/10.2165/00002512-199404030-00005

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