NO mediates postjunctional inhibitory effect of neurogenic ACh in guinea pig small intestinal microcirculation

The present study was designed to evaluate the role of the endothelium as a n effector organ of neurally mediated inhibition of vascular tone. Acetyl c holine (ACh), either released by stimulation of the submucosal ganglia or a pplied exogenously, inhibited phenylephrine (PE)-induced constrictions in a rterioles of the guinea pig intestinal submucosa. N-G-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, attenuated the resp onse to superfused ACh by 74% compared with 94% attenuation obtained with N -G-nitro-L-arginine (L-NNA). L-NNA attenuated the response to neurally rele ased ACh by 98% and that to iontophoretically applied ACh by 92%. L-Arginin e reversed the effects of both L-NMMA and L-NNA. Functional integrity of th e endothelium was essential for the neurally mediated inhibition of PE-indu ced constrictions. However, neurogenic inhibition of neurally evoked constr ictions was preserved despite endothelial disruption. It was concluded that at the postjunctional level, the mechanism of action of neurally released ACh was almost exclusively via a NO-dependent pathway with the source of NO being the vascular endothelium.