NONADRENERGIC-NONCHOLINERGIC RELAXATIONS OF ISOLATED CIRCULAR MUSCLE FROM SOUTH-AMERICAN OPOSSUM ESOPHAGOGASTRIC JUNCTION - IS NITRIC-OXIDETHE INHIBITORY MEDIATOR

Nonadrenergic-noncholinergic (NANC) inhibitory nerves are responsible for most of the nerve induced relaxations of gastrointestinal muscle. It has recently been proposed that NANC nerves may release nitric oxid e (NO) or a related compound derived from L-arginine. We have recently shown that the South American (SA) opossum is another suitable model to elucidate the mechanism involved in these NANC relaxations. In the present study the effect of NO synthase inhibitors as well as NO inact ivators on the NANC-nerve induced relaxations of the circular muscle o f the esophagogastric junction (EGJ) of the SA opossum was investigate d. It was observed that the NO synthase inhibitors, L-NOARG and L-NAME , caused a concentration-dependent reduction of NANC-nerve induced rel axations which was reversed by L-but not D-arginine. The NO-donors sod ium nitroprusside and hydroxilamine as well as NO caused concentration -dependent relaxations of the EGJ circular muscle. In the myenteric pl exus of this region, NADPH-diaphorase positive neurons and nerve fiber s were observed while in the circular muscle layer only numerous posit ive fibers were found. The NO inactivators, hydroquinone, pyrogallol a nd carboxy-PTIO, reduced NO-induced relaxations but failed to affect N ANC nerve-and sodium nitroprusside-induced relaxations. Taken together , these findings indicate that NANC nerve induced relaxation of the SA opossum EGJ circular muscle is dependent on neural NO synthase activi ty and suggest that the neurotransmitter being released is a superoxid e resistant molecule, which is unlikely to be the NO radical, or that the activity of NO synthase is required for the release of the actual neurotransmitter rather than for synthesizing the neuromediator. (C) 1 997 Elsevier Science B.V.