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 branche s and investigates the mechanisms of inhibitory and potentiating endothelin -1-effects. In basilar arteries, endothelin-1 reduces the contractions indu ced by 5-hydroxytryptamine (5-HT), by the thromboxane A(2) agonist U46619, and by vasopressin. The inhibitory effect of endothelin-l on the contractio n induced by 5-HT is abolished by deendothelialization, by the endothelin E TB 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 ind uced by 5-HT is only somewhat modified by deendothelialization, but abolish ed by the thromboxane A(2) receptor antagonists GR32191 and ridogrel. U4661 9 potentiates the 5-HT-effect in mesenteric arteries. Thus, though the cont ractile endothelin ETA receptors were not blocked, threshold concentrations of endothelin-1 inhibited contractile effects in the rat basilar artery vi a activation of endothelial ETB receptors. Prostaglandins and ATP-sensitive K+ channels are involved in this inhibitory action. In contrast, endotheli n-1 potentiates contractile actions in mesenteric arteries via the release of endogeneous thromboxane A(2) from non-endothelial cells. The study point s out the completely different role of the endothelium in combined effects of endothelin-1 between cerebral and mesenteric arteries.