Threshold concentrations of endothelin-1: the effects on contractions induced by 5-hydroxytryptamine in isolated rat cerebral and mesenteric arteries

• Published in: Pharmacology & toxicology Vol. 85; no. 3; p. 115
• Main Authors: Hempelmann, R G, Pradel, R H, Mehdorn, H M, Ziegler, A
• Format: Journal Article
• Language: English
• Published: Denmark 01.09.1999
• Subjects: 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid - pharmacology; Animals; Basilar Artery - drug effects; Basilar Artery - physiology; Biphenyl Compounds - pharmacology; Drug Synergism; Endothelin Receptor Antagonists; Endothelin-1 - pharmacology; Glyburide - pharmacology; Heptanoic Acids - pharmacology; Indomethacin - pharmacology; Male; Mesenteric Arteries - drug effects; Mesenteric Arteries - physiology; Muscle Contraction - drug effects; Muscle Contraction - physiology; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - physiology; Pentanoic Acids - pharmacology; Peptides, Cyclic - pharmacology; Pyridines - pharmacology; Rats; Rats, Sprague-Dawley; Serotonin - pharmacology; Vasoconstriction - drug effects; Vasopressins - pharmacology
• ISSN: 0901-9928
• DOI: 10.1111/j.1600-0773.1999.tb00077.x

This study compares the effects of threshold concentrations of endothelin-1 in isolated rat basilar arteries with those in mesenteric arterial branches and investigates the mechanisms of inhibitory and potentiating endothelin-1-effects. In basilar arteries, endothelin-1 reduces the contractions induced by 5-hydroxytryptamine (5-HT), by the thromboxane A2 agonist U46619, and by vasopressin. The inhibitory effect of endothelin-1 on the contraction induced by 5-HT is abolished by deendothelialization, by the endothelin ET(B) receptor antagonist RES 701-1, by indomethacin, or by glibenclamide. In mesenteric arteries, endothelin-1 potentiates the contractile effects of 5-HT, U46619, and vasopressin. The potentiation of the contractile effect induced by 5-HT is only somewhat modified by deendothelialization, but abolished by the thromboxane A2 receptor antagonists GR32191 and ridogrel. U46619 potentiates the 5-HT-effect in mesenteric arteries. Thus, though the contractile endothelin ET(A) receptors were not blocked, threshold concentrations of endothelin-1 inhibited contractile effects in the rat basilar artery via activation of endothelial ET(B) receptors. Prostaglandins and ATP-sensitive K+ channels are involved in this inhibitory action. In contrast, endothelin-1 potentiates contractile actions in mesenteric arteries via the release of endogeneous thromboxane A2 from non-endothelial cells. The study points out the completely different role of the endothelium in combined effects of endothelin-1 between cerebral and mesenteric arteries.