SUPPRESSION OF CEREBRAL VASODILATION WITH ENDOTHELIN-1

We investigated the effect of endothelin-1 on relaxation responses induced by vasodilator substances in canine middle cerebral arteries to better understand regulation of cerebrovascular tone and its potential impact on mechanism of cerebral vasospasm. Endothelin-1 elicited concentration-dependent contractions in helical strips of canine cerebral arteries (EC50; 4.62 X 10(-9) M). Pretreatment with 10(-9) M endothelin-1 significantly reduced endothelium-dependent relaxation elicited by substance P and endothelium-independent relaxations by nitroglycerin, prostaglandin I-2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-indipendent relaxations, it did inhibit endothelium-dependent relaxation caused by substance P. A low concentration (10(-10) M) of endothelin-1 also significantly reduced endothelium-dependent relaxation of canine mesenteric arteries induced by acetylcholine. Other vasoconstrictor peptides such as angiotensin-II and vasopressin did not inhibit endothelium-dependent and -independent relaxations. These results indicate that endothelin-1 not only produces cerebral vasoconstriction but also interferes with vasodilator mechanisms and that endothelium-dependent vasodilation is more sensitive to the inhibitory effect of endothelin-1 than endothelium-independent vasodiltion.