INHIBITION OF NITROXIDERGIC NERVE FUNCTION BY NEUROGENIC ACETYLCHOLINE IN MONKEY CEREBRAL-ARTERIES

1. Modification hy endogenous or exogenous acetylcholine and vasoactiv e intestinal polypeptide (VIP) of vasodilatation mediated by nitric ox ide (NO) released from nitroxidergic nerves was studied in isolated mo nkey cerebral arteries. In arterial strips denuded of endothelium, tra nsmural electrical stimulation (2-20 Hz) produced relaxations that wer e abolished by tetrodotoxin. 2. The relaxation response was attenuated by acetylcholine, and the attenuation was reversed by atropine. Atten uation was also observed with AP-DX 116, an antagonist of the muscarin ic acetylcholine receptor subtype, M(2). NO-induced relaxation was not affected by acetylcholine. Neurogenic relaxation was also inhibited b y physostigmine and potentiated by atropine. 3. VIP in concentrations that elicited slight relaxation did not alter the response to nerve st imulation. In the strips showing tachyphylaxis to VIP, the neurogenic response was not inhibited. 4. Histochemical studies of whole-mount pr eparations revealed nerve fibres with NO synthase and VIP immunoreacti vity, and also acetylcholinesterase, suggesting the presence of periva scular nitroxidergic, VIPergic and cholinergic innervation. 5. It is c oncluded that the actions of nitroxidergic nerve fibres on the monkey cerebral artery are inhibited by nerve-released acetylcholine acting o n prejunctional muscarinic receptors, possibly of the M(2) subtype. De spite the presence of VIP immunoreactive nerve fibres and the ability of exogenous VIP to relax the artery, there is no evidence supporting either a prejunctional modulation of nitroxidergic nerve function by V IP or a role for VIP as a vasodilatory neurotransmitter.