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.
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Prostaglandins ATP K+ thromboxane A2 5-hydroxytryptamine 5-HT thromboxane A2 U46619 vasopressin 5-HT RES 701-1 indomethacin glibenclamide 5-HT U46619 vasopressin 5-HT thromboxane A2 GR32191 ridogrel U46619 5-HT 5-hydroxytryptamine endothelin-1 endothelial ET(B) receptors ATP-sensitive K+ channels endothelin-1 endothelin-1 endothelin-1 endothelin-1 vasopressin endothelin-1 endothelin ET(B) receptor endothelin-1 endothelin-1 vasopressin thromboxane A2 receptor endothelin ET(A) receptors endothelin-1