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.
Matthew
J D
JD
Department of Physiology and Pharmacology, University of Strathclyde, Glasgow, Scotland.
Wadsworth
R M
RM
D000813:Anilides; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002536:Cerebral Arteries / Q000187:drug effects / Q000294:innervation*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology*; D012756:Sheep; D013482:Superoxide Dismutase / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects; D020866:omega-Conotoxin GVIA
D000813:Anilides; D002121:Calcium Channel Blockers; D004791:Enzyme Inhibitors; D010455:Peptides; D019335:Nitroarginine; D009569:Nitric Oxide; C080840:N(G)-nitroarginine-4-nitroanilide; D020866:omega-Conotoxin GVIA; D001120:Arginine; D019001:Nitric Oxide Synthase; D013482:Superoxide Dismutase