Threshold concentrations of endothelin-1: the effects on contractions induced by 5-hydroxytryptamine in isolated rat cerebral and mesenteric arteries.
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.
Hempelmann
R G
RG
Department of Neurosurgery, University of Kiel, Germany.
Pradel
R H
RH
Mehdorn
H M
HM
Ziegler
A
A
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000502:physiology; D001713:Biphenyl Compounds / Q000494:pharmacology; D004357:Drug Synergism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D005905:Glyburide / Q000494:pharmacology; D006538:Heptanoic Acids / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D010421:Pentanoic Acids / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects; D014667:Vasopressins / Q000494:pharmacology
D001713:Biphenyl Compounds; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D006538:Heptanoic Acids; D010421:Pentanoic Acids; D010456:Peptides, Cyclic; D011725:Pyridines; D014667:Vasopressins; C087120:RES 701-1; D012701:Serotonin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C060013:vapiprost; C060219:ridogrel; C072247:cyclo(Trp-Asp-Pro-Val-Leu); D005905:Glyburide; D007213:Indomethacin