Central vagal activation by an analogue of trh stimulates gastric nitric oxide release in rats. Saperas, Esteban, M. D., Marisabel Mourelle, Ph. D., Javier Santos, M. D., Salvador Moncada, Frs, Juan-R. Malagelada, M. D. Digestive System Research Unit, Hospital General Vall d'Hebron, Autonomous University of Barcelona, Spain and Wellcome Laboratories,UK.
APStracts 2:0003G, 1995.
Central vagal activation by an analogue of TRH stimulates gastric nitric oxide release in rats. Saperas E., M. Mourelle, J. Santos, S. Moncada and J-R. Malagelada. In the stomach, nitric oxide (NO) appears to be involved in vagally induced cholinergic vasodilation and non-adrenergic, non-cholinergic (NANC) relaxation of the fundus. We investigated whether central vagal activation by intracisternal (ic) injection of a TRH analogue stimulates gastric NO release in anesthetized rats. To quantitate gastric NO production, the luminal release of NO breakdown products, nitrite (NO2-) and nitrate (NO3-), were measured by the Griess_ method. Intracisternal injection of RX 77368 (30 - 300 ng) dose-dependently stimulated gastric NO2-/NO3- release (p< 0.05) along with a significant acid secretory response (p< 0.05). The specific inhibitor of NO synthesis, L-NAME (10 mg/kg ip) completely blocked gastric luminal NO2-/NO3- release without affecting the acid secretory response to the highest dose of RX 77368. Either bilateral cervical vagotomy, hexamethonium (15 mg/kg ip) or atropine (1 mg/kg ip) abolished both gastric luminal release of NO-derived metabolites and the acid secretory responses to RX 77368. These results indicate that intracisternal injection of RX 77368 stimulates gastric release of NO through vagal nicotinic pathways, and peripheral activation of muscarinic receptors. These findings provide evidence for central nervous system (CNS) regulation of nitric oxide-mediated functions in the rat stomach through TRH-sensitive vagal pathways. 

Received 28 March 1994; accepted in final form 6 January 1995.
APS Manuscript Number G117-4.
Article publication pending Am. J. Physiol. (Gastrointest. Liver Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 February 1995.