Nitric oxide control of toad mesenteric vasculature

This study determined the role of nitric oxide (NO) in neurogenic vasodilation in mesenteric resistance arteries of the toad, Bufo marinus. Nitric oxide synthase (NOS) was anatomically demonstrated only in perivascular nerves but not the endothelium. Acetylcholine (ACh) and nicotine caused tetrodotoxin (TTX)-sensitive neurogenic vasodilation of mesenteric arteries. The ACh-induced vasodilation was endotheliumindependent and was mediated by the NO/soluble guanylyl cyclase (GC) signalling pathway, as the vasodilation was blocked by the soluble GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3a]quinoxalin-1-one (ODQ), and the NOS inhibitors, N-Nitro-L-arginine methyl ester (LNAME) and N-Nitro-L-arginine (L-NNA). Furthermore, the ACh-induced vasodilation was significantly decreased by the more selective neural NOS (nNOS) inhibitor, N-(1-Imino-3butenyl)-L-ornithine (vinyl-L-NIO). The nicotine-induced vasodilation was endotheliumindependent and mediated by NO and calcitonin gene-related peptide (CGRP), as pretreatment of mesenteric arteries with a combination of L-NNA and the CGRP receptor antagonist, CGRP(8-37), blocked the vasodilation. Clotrimazole significantly decreased the ACh-induced response, providing evidence that a component of the NO vasodilation involved either calcium-activated potassium (KCa) or voltage-gated potassium (KV) channels. These data show that NO control of mesenteric resistance arteries of toad is provided by nitrergic nerves rather than the endothelium, and implicate NO as a potentially important regulator of gut blood flow and peripheral blood pressure.