Capsaicin-induced gastric hyperemia and protection are NO- dependent.
Topical treatment of gastric mucosa with capsaicin (cap) increases gastric mucosal blood flow (GMBF) and protects the mucosa from injury by acidified bile salts. The purpose of this study was to test the hypothesis that this hyperemia related "cytoprotection" is mediated by nitric oxide. Male Sprague-Dawley rats were anesthetized and the glandular stomach (blood supply intact) was chambered between two plastic rings. 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 inhibitor, 5 min prior to baseline treatment, followed by a 15-min preinjury period of saline and a 15-min injury period of 10 mM acidified taurocholate (ATC, pH 1.2). Groups 3 and 4 were treated as above except topical cap (160 microM) 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). Baseline 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 exposure was 42 +/- 4 and 22 +/- 2 in groups 3 and 4, respectively. Graded histologic and gross injuries were significantly worse in group 4 compared to group 3 (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
Podolsky
R S
RS
Department of Surgery, Pennsylvania Hospital, Philadelphia 19107.
Grabowski
M
M
Milner
R
R
Ritchie
W P
WP
Dempsey
D T
DT
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002211:Capsaicin / Q000494:pharmacology*; D005753:Gastric Mucosa / Q000098:blood supply* / Q000187:drug effects; D006940:Hyperemia / Q000139:chemically induced*; D017078:Laser-Doppler Flowmetry; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D013272:Stomach Diseases / Q000473:pathology / Q000517:prevention & control*; D013656:Taurocholic Acid / Q000494:pharmacology*
D009569:Nitric Oxide; D013656:Taurocholic Acid; D001120:Arginine; D002211:Capsaicin; D019331:NG-Nitroarginine Methyl Ester