HALOTHANE AND ISOFLURANE ATTENUATE THE RELAXANT RESPONSE TO NONADRENERGIC AND NONCHOLINERGIC NERVE-STIMULATION OF ISOLATED CANINE CEREBRAL-ARTERIES

Stimulation of nonadrenergic noncholinergic (NANC) nerves elicits rela xation of canine cerebral arteries via the nitric oxide (NO)-cGMP path way. The purpose of this study was to investigate the effects of halot hane and isoflurane on the relaxant response of isolated canine cerebr al arteries to NANC nerve stimulation. The isometric tension of isolat ed canine cerebral arteries, which had been denuded of endothelium, wa s measured in a tissue bath. The application of transmural electrical stimulation (TES) at a frequency of 5 Hz elicited a transient relaxati on of arteries partially contracted with prostaglandin F-2 alpha. This effect was abolished by treatment with N-G-nitro-L-arginine (3 x 10(- 5) M), 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (10(-5) M), or tetr odotoxin (10(-6) M). Treatment with halothane (2.3%) or isoflurane (2. 3% and 3.5%) attenuated the relaxant response to TES (P < 0.05). Halot hane (2.3%) but not isoflurane (2.3% and 3.5%) attenuated relaxation i nduced by s-nitro-N-acetylpenicillamine. We suggest that halothane and isoflurane inhibit cerebroarterial vasodilation mediated via NO-cGMP pathway activated by stimulation of the NANC nerves. The sites of acti on of halothane and isoflurane on the NO-cGMP pathway may differ. Impl ications: Nonadrenergic noncholinergic nerves play a role in the regul ation of vascular tone in cerebral arteries via the nitric oxide-cGMP pathway. This study showed that, in isolated canine cerebral arteries, halothane and isoflurane inhibit the relaxation caused by nonadrenerg ic noncholinergic nerve stimulation, but their sites of action may dif fer.