IN-VITRO AND IN-VIVO EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITORS AND NITRIC-OXIDE INACTIVATORS ON THE SOUTH-AMERICAN OPOSSUM ILEOCOLONIC JUNCTION

The potential role of nitrergic nerves in the regulation of the South American (SA) opossum ileocolonic junction (ICJ) function was investig ated. In vitro, the effects of nitric oxide (NO) synthase inhibitors a nd NO inactivators on the non-adrenergic noncholinergic (NANC) nerve-m ediated relaxations of the circular muscle of the SA opossum ICI were determined by employing isolated strips. Electrical field stimulation (0.2-8.0 Hz) caused frequency-dependent NANC relaxations. Nicotine and ATP also induced concentration dependent NANC relaxations that were a bolished by tetrodotoxin (TTX). The relaxation response induced by NAN C nerve activation was reduced in a dose dependent manner by NO syntha se inhibitors while vasoactive intestinal peptide (VIP) and sodium nit roprusside (SNP) induced relaxations were uninfluenced by these drugs, in vivo, the NO synthase inhibitor, L-NAME, administered into the loc al artery caused a raise in intraluminal pressure of the ICJ in anaest hetized SA opossums in a L-arginine-preventable manner. Hydroquinone a nd pyrogallol, while being able to reduce, in a superoxide dimutase (S OD) reversible manner, the relaxations induced by exogenous NO failed to affect the NANC nerve-induced relaxations. Finally, neurones and ne rve fibres in the myenteric plexus as well as varicose nerve fibres on the circular smooth layer were positive for NADPH-diaphorase activity . These findings indicate that nitrergic nerves inhibit ICJ circular s mooth muscle in vitro and in vivo but cast doubts on the nemomediator being the NO radical.