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 ne urotransmission and its potential release mechanism in sheep isolated middle cerebral artery rings was investigated using NO synthase inhibi tors, haemolysate, superoxide dismutase (SOD) and omega-conotoxin GVIA . In the presence of guanethidine (5 mu M) and atropine (2 mu M), tran smural nerve stimulation of precontracted artery rings elicited an end othelium independent vasodilator response that could be abolished by t etrodotoxin. 2. The magnitude of the vasodilator response was virtuall y abolished by N-G-nitro-L-arginine-p-nitroanilide (L-NAPNA; 100-500 m u M) and significantly reduced by N-G-nitro-L-arginine (50 mu M) or ha emolysate (1 mu l ml(-1)). N-G-nitro-D-arginine (50 mu M) had no effec t. In the presence of the NO synthase inhibitors, addition of L-argini ne (300 mu M) produced either no effect or a partial, transient restor ation of inhibitor responses following electrical field stimulation (E FS). 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 relaxat ion elicited by transmural nerve stimulation. 3. Superoxide dismutase (SOD; 150 U ml(-1)) did not produce any significant changes in the mag nitude of the EFS induced vasodilation. Thus, superoxide anions appear not to be a limiting factor for NO-mediated neurogenic vasodilation i n sheep MCA. 4. omega-Conotoxin GVIA (100 nM) caused an almost immedia te abolition of the EFS-induced vaso-constrictor response at resting t ension, but had no effect on the vasodilator response at all frequenci es of stimulation (0.5-8 Hz) tested. Thus, the neurotransmission proce ss mediating this vasodilator response does not appear to involve Ca2 entry via N type Ca2+ channels. Copyright (C) 1997 Elsevier Science I nc.