1. The involvement of nitric oxide (NO) as a mediator of inhibitory neurotransmission and its potential release mechanism in sheep isolated middle cerebral artery rings was investigated using NO synthase inhibitors, haemolysate, superoxide dismutase (SOD) and omega-conotoxin GVIA. In the presence of guanethidine (5 mu M) and atropine (2 mu M), transmural nerve stimulation of precontracted artery rings elicited an endothelium independent vasodilator response that could be abolished by tetrodotoxin. 2. The magnitude of the vasodilator response was virtually abolished by N-G-nitro-L-arginine-p-nitroanilide (L-NAPNA; 100-500 mu M) and significantly reduced by N-G-nitro-L-arginine (50 mu M) or haemolysate (1 mu l ml(-1)). N-G-nitro-D-arginine (50 mu M) had no effect. In the presence of the NO synthase inhibitors, addition of L-arginine (300 mu M) produced either no effect or a partial, transient restoration of inhibitor responses following electrical field stimulation (EFS). L-NAPNA (100 mu M) did not affect the relaxant response to the NO donor SIN-1. These results suggest that NO is involved in the relaxation elicited by transmural nerve stimulation. 3. Superoxide dismutase (SOD; 150 U ml(-1)) did not produce any significant changes in the magnitude of the EFS induced vasodilation. Thus, superoxide anions appear not to be a limiting factor for NO-mediated neurogenic vasodilation in sheep MCA. 4. omega-Conotoxin GVIA (100 nM) caused an almost immediate abolition of the EFS-induced vaso-constrictor response at resting tension, but had no effect on the vasodilator response at all frequencies of stimulation (0.5-8 Hz) tested. Thus, the neurotransmission process mediating this vasodilator response does not appear to involve Ca2+ entry via N type Ca2+ channels. Copyright (C) 1997 Elsevier Science Inc.
