Mechanisms underlying the neurogenic relaxation in dog isolated hepatic arteries.
In canine hepatic arterial strips responding to nicotine with contraction, prazosin abolished the response or reversed it to a relaxation. Mechanisms underlying the relaxation were analyzed in hepatic and coronary arterial strips denuded of the endothelium and treated with prazosin and indomethacin. In the hepatic arterial strips precontracted with prostaglandin (PG) F2alpha, nicotine-induced relaxations were not influenced by atropine but were inhibited by timolol and abolished by hexamethonium. Treatment with [8-37] calcitonin gene-related peptide ([8-37] CGRP), a selective CGRP1-receptor antagonist, also attenuated the nicotine-induced relaxation, but a vasoactive intestinal polypeptide antagonist was without effect. Combined treatment with timolol and [8-37] CGRP depressed the response to a greater extent than either antagonist alone. The slight relaxation remaining under the combined treatment was abolished by NG-nitro-L-arginine (L-NA) and restored by L-arginine. In coronary arterial strips precontracted with PGF2alpha, nicotine produced a moderate relaxation, which was abolished or markedly inhibited by treatment with hexamethonium or timolol but was unaffected by L-NA. It is concluded that the nicotine-induced relaxation is mediated by norepinephrine, CGRP, and NO released from perivascular nerves in dog hepatic arterial strips; the responses associated with activations of beta-adrenoceptors and CGRP1 receptors are predominant over those to NO. The coronary arterial relaxation seems to be mediated by neurogenic norepinephrine but not by NO.
Shiraishi
S
S
Department of Pharmacology, Shiga University of Medical Science, Seta, Ohtsu, Japan.
Okamura
T
T
Kodama
M
M
Toda
N
N
D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology; D015237:Dinoprost / Q000494:pharmacology; D004285:Dogs; D005260:Female; D006499:Hepatic Artery / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology; D009538:Nicotine / Q000494:pharmacology
D009538:Nicotine; D015237:Dinoprost