Barbiturates inhibit endothelium-dependent and independent relaxations mediated by cyclic GMP.
The inhibitory effects of volatile and local, but not intravenous, anesthetics on endothelium-dependent relaxations of blood vessels have been demonstrated in vitro by several investigators. The aim of this study was to determine the effects of barbiturates on endothelium-dependent arterial relaxation and elucidate the mechanism(s) responsible. Canine mesenteric arteries and rat aortae were isolated, and tension changes in helical strips were recorded. Endothelium-dependent relaxations elicited by acetylcholine and bradykinin in canine mesenteric arteries, and those by acetylcholine in rat aortae, were significantly attenuated by thiopental (3 x 10(-4) M) pretreatment. Sodium nitroprusside (SNP)-induced, endothelium-independent relaxations were significantly attenuated by thiopental (10(-4)-3 x 10(-4) M). The effects of pentobarbital were less marked than those of thiopental. Acetylcholine (10(-5) M)-stimulated levels of 3',5'-cyclic guanosine monophosphate (cGMP) in rat aortae were reduced significantly by thiopental and pentobarbital (both 10(-3) M), and SNP (3 x 10(-7) M)-stimulated levels were reduced by thiopental (3 x 10(-4)-10(-3) M) and pentobarbital (10(-3) M). We conclude that barbiturates inhibit cGMP-mediated endothelium-dependent and independent arterial relaxations. Inhibition of endothelium-dependent relaxation by barbiturates may be mediated by their effects on vascular smooth muscle itself and not on endothelium.
Terasako
K
K
Department of Anesthesia, Kyoto University Hospital, Japan.
Nakamura
K
K
Toda
H
H
Kakuyama
M
M
Hatano
Y
Y
Mori
K
K
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D001920:Bradykinin / Q000494:pharmacology; D006152:Cyclic GMP / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D010424:Pentobarbital / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013874:Thiopental / Q000494:pharmacology*
D006152:Cyclic GMP; D010424:Pentobarbital; D013874:Thiopental; D000109:Acetylcholine; D001920:Bradykinin