Summary
(1) The actions of porcine endothelin (ET), an endothelium-derived vasoconstrictor peptide, have been investigated in several in vitro smooth and cardiac muscle preparation as well as on the blood pressure of anaesthetized rats and rabbits. (2) In isolated visceral smooth muscles (guinea pig ileum, rat colon and uterus, rabbit jejunum) ET caused a long-lasting contraction which persisted after repeated rinsing. ET did not interfere with the spontaneous phasic activity of the rabbit jejunum or with contractions evoked by histamine or carbachol. (3) ET contracted isolated blood vessels (portal vein of guinea-pig and rat). In isolated perfused organs (rabbit ear, guinea-pig lung, rat mesentery and hindpaw) ET led to a long-lasting vasoconstriction. In the isolated perfused guinea-pig lung ET caused vaso- and bronchoconstriction. (4) ET produced a long-lasting positive inotropic effect in spontaneously beating isolated guinea-pig atria. The positive inotropic action of strophanthin was augmented in the presence of ET. (5) In the isolated perfused guinea-pig and rat hearts the prominent effect of ET was a long-lasting coronary vasoconstriction. (6) Pithed rats responded to i.v. injection of ET with a long-lasting increase in blood pressure. In pentobarbitone anaesthetized rats pretreated either with atropine, with guanethidine plus atropine, or with guanethidine plus atropine plus indomethacin, the long-lasting increase in blood pressure was smaller than in pithed rats whereas the initial short-lasting decrease in blood pressure was more pronounced; in pentobarbitone anaesthetized rabbits endothelin caused bronchoconstriction, a decrease in blood pressure and a pronounced increase in central venous pressure possibly resulting from pulmonary or coronary artery constriction or a combination of both effects. (7) Neither topical nor systemic application of ET influenced the bleeding time from small rat mesenteric arteries. (8) The general effect of ET on visceral, bronchial and vascular smooth muscles was a longlasting contraction. Despite its general constrictor potency seen in isolated vascular preparations ET can cause a transient decrease in arterial blood pressure in anaesthetized rats and rabbits. The role of ET when released from vascular endothelium remains a matter of speculation.
Similar content being viewed by others
References
Antunes E, DeNucci G, Vane JR (1988) Endothelin releases cicosanoids from and is removed by isolated perfused lungs of the guinea-pig. J Physiol 407:40P
Baydoun AR, Peers SH, Cirino G, Woodward B (1989) The effects of endothelin in the isolated perfused rat heart. Br J Pharmacol 9:98P
Brain SD, Tippins JR, Williams TJ (1988) Endothelin produces potent microvascular constriction. Br J Pharmaol 95:1005–1007
De Mey JG, Vanhoutte PM (1983) Anoxia and endothelium-dependent reactivity of the canine femoral artery. J Physiol 335:65–74
Finet M, de Nucci G, Willoughby DA, Vane JR (1989) The roles of endothelium and calcium in endothelin-induced contractions of the rat isolated aorta. Br J Pharmacol 46:C128
Firth JD, Ratcliffe PJ, Raine AEG, Ledingham JGG (1988) Endothelin: An important factor in acute renal failure. Lancet:1179–1182
Furchgott RE, Zawadski J (1980) The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288:373–376
Gaddum JH, Lembeck F (1949) The assay of substances from the adrenal medulla. Br J Pharmacol 4:401–408
Gillespie MN, Owasoyo JO, McMurty IF, O'Brien RF (1986) Sustained coronary vasoconstriction provoked by a peptidergic substance released from endothelial cells in culture. J Pharmacol Exp Ther 236:339–343
Han SP, Trapani AJ, Fak KF, Westfall TC, Knuepfer MM (1989) Effects of endothelin on regional hemodynamics in conscious rats. Eur J Pharmacol 159:303–305
Hickey KA, Rubanyi G, Paul RJ, Highsmith RF (1985) Characterization of a coronary vasoconstrictor produced by cultured endothelial cells. Am J Physiol 248:C550-C556
Hu RJ, von Harsdorf R, Lang RF (1988) Endothelin has potent inotropic effects in rat atria. Eur J Pharmacol 158:275–278
Ishikawa T, Yanagisawa M, Kimura S, Goto K, Masaki T (1988) Positive inotropic action of novel vasoconstrictor peptides endothelin on guinea pig atria. Am J Physiol 255:H970-H973
Itoh Y, Yanagisawa M, Ohkubo S,Kimura C, Kasaka T, Inoue A, Ishida N, Mitsui Y, Onda H, Fujino M, Masaki T (1988) Cloning and sequence analysis of cDNA encoding the precursor of a human endothelium-derived vasoconstrictor peptide, endothelin: identity of human and porcine endothelin. FEBS 231:440–444
Le Monnier de Gouville AC, Cavero I (1989) Haemodynamic and pharmacological profile of endothelin in pithed rats. Br J Pharmacol 96:95P
Lee CY, Chiappinelli VA (1988) Similarity of endothelin to snake venom toxin. Nature 335: (letter)
Lembeck F (1954) Über den Nachweis von 5-Oxytryptamin (Enteramin, Serotonin) in Carcinoidmetastasen. Arch exper Path Pharmacol 221:50–66
Maggi CA, Patacchini R, Giulliani S, Meli A (1989) Potent contractile effect of endothelin in isolated guinea-pig airways. Eur J Pharmacol 160:179–182
McGregor DD (1965) The effect of sympathetic nerve stimulation on vasoconstrictor responses in perfused mesenteric blood vessels of the rat. J Physiol 177:21–30
Minkes RK, Kadowitz PJ (1989) Influence of endothelin on systemic arterial pressure and regional blood flow in the cat. Eur J Pharmacol 163:163–166
O'Brien RF, Robbins RJ, McMurty I (1987) Endothelial cells in culture produce a vasoconstrictor substance. J Cell Physiol 132:263–270
Payne AN, Whittle BJR (1988) Potent cyclo-oxygenase-mediated bronchoconstrictor effects of endothelin in the guinea-pig in vivo. Eur J Pharmacol 158:303–304
Rubanyi GM, Vanhoutte PM (1985) Hypoxia releases a vasoconstrictor substance from canine vascular endothelium. J Physiol 364:45–56
Saria A, Theodorsson-Norheim E, Gamse R, Lundberg JM (1985) Release of substance P and substance K-like immunoreactivities from the isolated perfused guinea-pig lung. Eur J Pharmacol 106:207–208
Shipley RE, Tilden JN (1947) A pithed rat preparation suitable for assaying pressor substances. Proc Soc Exp Biol (NY) 64:453–457
Takasaki C, Yanagisawa M, Kimura S, Goto K, Mosaki T (1988) Similarity of endothelin to snake venom toxin. Nature 335:303 (letter)
Tippins JR, Antoniw JW (1989) Effect of endothelin on canine and porcine coronary preparations in vitro. Br J Pharmacol 96:100P
Uchida Y, Ninomiya H, Saotome M, Nomura A, Ohtsuka M, Yanagisawa M, Goto K, Masaki T, Hasegawa S (1988) Endothelia a novel vasoconstrictor peptide, as potent bronchoconstrictor. Eur J Pharmacol 154:227–228
Unger T, Photiadia J, Rohmeiss S, Rohmeiss P (1989) Endothelin: Hemodynamic characterization in conscious rats. Naunyn-Schmiedeberg's Arch Pharmacol 339 (Suppl):R65
Vanhoutte PM (1987) Endothelium dependent contractions in arteries and veins. Blood vessels 24:141–144
Warner T, De Nucci G, Vane JR (1988) Release of EDRF by endothelin in the rat isolated perfused mesentery. Br J Pharmacol 95:723P
Wright CE, Fozard JR (1988) Regional vasodilation is a prominent feature of the haemodynamic response to endothelin in anaesthetized, spontaneously hypertensive rats. Eur J Pharmacol 155:201–203
Yanagisawa M, Kurihara H, Kimura S, Tomobe Y, Kobayashi M, Mitsui Y, Goto K, Masaki T (1988) A novel potent vasoconstrictor peptide produced by endothelial cells. Nature 332:411–415
Yanagisawa M, Inoue A, Ishikawa T, Kasuya Y, Kimura S, Kumagaye S, Nakajima K, Watanabe TX, Sakakibara S, Goto K, Masaki T (1988) Primary structure, synthesis, and biological activity of rat endothelin, an endothelium-derived vasoconstrictor peptide. Proc Natl Acad Sci USA 85:6964–6967
Zawilska K, Born GVR, Begent NA (1982) Effect of ADP-utilizing enzymes on the arterial bleeding time in rats and rabbits. Br J Haematol 50:317–325
Author information
Authors and Affiliations
Additional information
Send offprint requests to F. Lembeck at the above address
Rights and permissions
About this article
Cite this article
Lembeck, F., Decrinis, M., Pertl, C. et al. Effects of endothelin on the cardiovascular system and on smooth muscle preparations in different species. Naunyn-Schmiedeberg's Arch Pharmacol 340, 744–751 (1989). https://doi.org/10.1007/BF00169684
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00169684