CAPSAICIN-INDUCED GASTRIC HYPEREMIA AND PROTECTION ARE NO- DEPENDENT

Topical treatment of gastric mucosa with capsaicin (cap) increases gas tric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypoth esis that this hyperemia related ''cytoprotection'' is mediated by nit ric oxide. Male Sprague-Dawley rats were anesthetized and the glandula r stomach (blood supply intact) was chambered between two plastic ring s. Animals were divided into four groups. All groups received a 5-min topical saline exposure. Groups 1 and 2 received iv saline or nitro-L- arginine methyl ester (L-NAME, 25 mg/kg iv), a specific nitric oxide i nhibitor, 5 min prior to baseline treatment, followed by a 15-min prei njury period of saline and a 15-min injury period of 10 mM acidified t aurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 mu M) was used during the preinjury period. GMBF was measured with a laser Doppler flowmeter (ml/min/100 g tissue). Injury was assessed grossly (grade 0-3), histologically (grade 0-3), and by measuring DNA content of a 5-min N-acetylcysteine wash (DNAE). Baselin e GMBF of 30 +/- 1.5 significantly decreased to 15 +/- 1.2 in group 1 versus group 2 (P < 0.05). When topical ATC was used GMBF increased to 59 +/- 4.9 and 25 +/- 2.8, respectively. Injury by grade and DNAE was not significantly different between these groups. GMBF during cap exp osure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Grade d histologic and gross injuries were significantly worse in group 4 co mpared to group 3 (P < 0.05). L-NAME blocked the hyperemic response to capsaicin and negated its protective effect. Nitric oxide is an impor tant mediator of the gastric mucosal hyperemic response to capsaicin, whose protective effect is preinjury blood flow dependent. (C) 1994 Ac ademic Press, Inc.