NITRIC-OXIDE PATHWAY IN CAT ESOPHAGUS - LOCALIZATION OF NITRIC-OXIDE SYNTHASE AND FUNCTIONAL-EFFECTS

In the cat lower esophageal sphincter (LES) and esophageal body, nitri c oxide synthase (NOS) immunoreactive nerves were abundant in the circ ular smooth muscle layer, especially in the LES region. NADPH diaphora se staining showed an identical pattern. The ability to form L-citrull ine from L-arginine corresponded roughly to the distribution of NOS. C onfocal microscopic analysis indicated colocalization within neurons o f vasoactive intestinal peptide (VIP) in 65% of NOS-positive nerves. I n LES circular smooth muscle preparations, electrically induced relaxa tions (single train stimuli) were generally abolished by NG-nitro-L-ar ginine (L-NNA). Continuous electrical stimulation for 2 min evoked a r elaxation in the presence of L-NNA. This relaxation was inhibited by V IP antiserum and followed by a decrease in guanosine 3',5'-cyclic mono phosphate, but not by any consistent change in adenosine 3',5'-cyclic monophosphate levels. K+ (124 mM) induced a biphasic relaxation, with L-NNA inhibiting the first phase but not the second. We conclude that nitric oxide (NO) has a major role as the mediator responsible for rel axation in the cat esophagus. NO seems also to initiate the release an d enhance the effect of another transmitter.