Cigarette smoking delays ulcer healing: role of constitutive nitric oxide synthase in rat stomach.
Epidemiological studies have shown that cigarette smoking is associated with peptic ulceration. This study aims to investigate the mechanisms by which cigarette smoking delays ulcer healing in rats. Gastric ulcers were induced by applying acetic acid to the luminal surfaces in rats. Twenty-four hours later, rats were exposed to different concentrations of cigarette smoke (0, 2, or 4%) for a 1-h period once daily for 3 or 6 days. Cigarette smoke exposure delayed ulcer healing and decreased gastric blood flow and angiogenesis at the ulcer margin. These changes were accompanied by a significant reduction of constitutive nitric oxide synthase (cNOS) activity but not PGE2 production and vascular endothelial growth factor levels. Administration of L-arginine (10 mg/kg iv) completely reversed the adverse actions on ulcer healing, gastric blood flow, and angiogenesis in the mucosa at the ulcer margin but partially restored angiogenesis in granulation tissues. In conclusion, cigarette smoke exposure delays ulcer healing through depression of gastric blood flow and angiogenesis at the ulcer margin. Reduction of cNOS expression and activity is suggested to be involved in these ulcerogenic processes.
Ma
L
L
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, Hong Kong, People's Republic of China.
Chow
J Y
JY
Cho
C H
CH
D000818:Animals; D001120:Arginine / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism; D004326:Drinking / Q000502:physiology; D004435:Eating / Q000502:physiology; D016228:Endothelial Growth Factors / Q000378:metabolism; D005753:Gastric Mucosa / Q000098:blood supply / Q000378:metabolism; D006097:Granulation Tissue / Q000098:blood supply; D008222:Lymphokines / Q000378:metabolism; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology*; D052250:Nitric Oxide Synthase Type III; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012907:Smoking; D013270:Stomach / Q000098:blood supply / Q000201:enzymology*; D013276:Stomach Ulcer / Q000378:metabolism / Q000503:physiopathology*; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D015430:Weight Gain / Q000502:physiology; D014945:Wound Healing / Q000502:physiology*
D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D001120:Arginine; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D015232:Dinoprostone