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 an effector organ of neurally mediated inhibition of vascular tone. Acetylcholine (ACh), either released by stimulation of the submucosal ganglia or applied exogenously, inhibited phenylephrine (PE)-induced constrictions in arterioles of the guinea pig intestinal submucosa. N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of nitric oxide (NO) synthesis, attenuated the response 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 released ACh by 98% and that to iontophoretically applied ACh by 92%. L-Arginine reversed the effects of both L-NMMA and L-NNA. Functional integrity of the endothelium was essential for the neurally mediated inhibition of PE-induced constrictions. However, neurogenic inhibition of neurally evoked constrictions 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.
Kotecha
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Department of Physiology, Monash University, Clayton, Victoria 3168, Australia. Neela.Kotecha@med.monash.edu.au
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D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology / Q000502:physiology*; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects; D004558:Electric Stimulation; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005724:Ganglia / Q000502:physiology; D006168:Guinea Pigs; D007421:Intestine, Small / Q000098:blood supply* / Q000294:innervation*; D007478:Iontophoresis; D008297:Male; D008833:Microcirculation / Q000502:physiology; D009420:Nervous System / Q000378:metabolism; D009569:Nitric Oxide / Q000502:physiology*; D019335:Nitroarginine / Q000494:pharmacology; D010890:Pirenzepine / Q000494:pharmacology; D014661:Vasoconstriction / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019335:Nitroarginine; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D010890:Pirenzepine; D001120:Arginine; D000109:Acetylcholine