Endothelium-dependent and -independent responses to vasodilators of isolated dog cerebral arteries.
We compared responses to calcium ionophore A23187, vasopressin, and substance P in helical strips of dog middle cerebral, basilar, and posterior communicating arteries to obtain a better understanding of humoral control of cerebrovascular tone in different brain regions and its potential impact on mechanisms of cerebral vasospasm. A23187 relaxed these different arterial strips partially precontracted with prostaglandin F2 alpha to a similar extent. Vasopressin produced concentration-dependent relaxation in basilar and posterior communicating arterial strips, whereas middle cerebral arterial strips either contracted or relaxed slightly. Relaxations induced by A23187 and vasopressin were either abolished or converted to contractions by removal of the endothelium. In contrast, the relaxation of cerebral arterial strips to substance P was markedly attenuated but not abolished by endothelium denudation; the remaining relaxation was suppressed by indomethacin. In some cerebral arterial strips with intact endothelium, substance P caused a transient contraction that was reversed to a relaxation by indomethacin or ONO-3708, a prostaglandin antagonist. In arterial strips denuded of endothelium from the same dogs, substance P always produced relaxations. Relaxations of cerebral arterial strips to A23187 and vasopressin appear to be mediated by endothelium-derived relaxing factor. The function of vasopressin receptors in endothelial cells differs markedly in basilar and posterior communicating arteries versus middle cerebral arteries. Substance P-induced relaxations appear to be primarily associated with endothelium-derived relaxing factor and with prostaglandin I2, whereas contractions appear to be mediated by endothelium-derived prostaglandins.
Onoue
H
H
Department of Pharmacology, Shiga University of Medical Sciences, Ohtsu, Japan.
Nakamura
N
N
Toda
N
N
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology*; D005260:Female; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008751:Methylene Blue / Q000494:pharmacology; D009994:Osmolar Concentration; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology*; D014667:Vasopressins / Q000494:pharmacology*
D014665:Vasodilator Agents; D014667:Vasopressins; D013373:Substance P; D000001:Calcimycin; D013928:Thromboxane A2; C049855:ONO 3708; D008751:Methylene Blue; D007213:Indomethacin