Cholinergic prejunctional inhibition of nitrergic neurotransmission in theguinea-pig isolated basilar artery (vol 26, pg 364, 1999)

1. The effects of endogenous and exogenous acetylcholine (ACh) on nitrergic relaxations elicited by electrical field stimulation (EFS) were studied in guinea-pig endothelium-denuded basilar artery preparations precontracted w ith 1 mu mol/L prostaglandin F-2 alpha and a possible role of K+ channels i n mediating the effects was investigated, 2. Acetylcholine (3 mu mol/L) and physostigmine (10 mu mol/L) produced smal l, yet statistically significant, inhibitions of EFS-induced nitrergic rela xations, while atropine (1 mu mol/L) slightly enhanced the nitrergic respon se. The ACh-induced inhibition was atropine sensitive. Acetylcholine or atr opine did not affect relaxations induced by sodium nitroprusside, 3, The inhibition of nitrergic relaxations by 3 mu mol/L ACh was prevented by the K+ channel blockers tetraethylammonium and 4-aminopyridine, but was not changed by iberiotoxin, apamin or glibenclamide, 4. Neither vasoactive intestinal polypeptide nor the alpha(2)-adrenoceptor agonists noradrenaline and clonidine modulated nitrergic neurotransmission in the guinea-pig basilar artery. 5. The findings show that ACh acts on prejunctional muscarinic receptors of nitrergic nerves to inhibit nitrergic neurotransmission. It is suggested t hat endogenous ACh may have this effect; however, the physiological signifi cance of this prejunctional modulation is not clear due to the relatively s mall effect produced. The prejunctional inhibitory action of ACh may involv e opening of neuronal K+ channels.