The role of nitric oxide in inhibitory neurotransmission in the middle cerebral artery of the sheep.

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 microM) and atropine (2 microM), 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 NG-nitro-L-arginine-p-nitroanilide (L-NAPNA; 100-500 microM) and significantly reduced by NG-nitro-L-arginine (50 microM) or haemolysate (1 microliter ml-1). NG-nitro-D-arginine (50 microM) had no effect. In the presence of the NO synthase inhibitors, addition of L-arginine (300 microM) produced either no effect or a partial, transient restoration of inhibitor responses following electrical field stimulation (EFS). L-NAPNA (100 microM) 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 Uml-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 vasoconstrictor 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.