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 I2, and KCl. Although endothelin-1 in a lower concentration (10(-10) M) did not affect these endothelium-independent 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.
Department of Neurosurgery, Jikei University School of Medicine, Tokyo, Japan.
N
N
Kaito
H
H
Onoue
T
T
Abe
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002536:Cerebral Arteries / Q000187:drug effects* / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000187:drug effects* / Q000502:physiology*; D004285:Dogs; D016232:Endothelins / Q000494:pharmacology* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000209:etiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D005996:Nitroglycerin / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D016232:Endothelins; D013373:Substance P; D011189:Potassium Chloride; D011464:Epoprostenol; D005996:Nitroglycerin; D000109:Acetylcholine