Mechanistic study of adverse actions of cigarette smoke exposure on acetic acid-induced gastric ulceration in rats.
Cigarette smoking is associated with peptic ulceration in humans. A mechanistic study of the potentiating effects of cigarette smoking on acetic acid-induced gastric ulceration in rats was hence performed. Rats were exposed to 0, 2 or 4% of cigarette smoke for three 1-hr periods during the 24 hr starvation before ulcer induction. Cigarette smoke exposure potentiated ulcer formation which was accompanied by a reduction of gastric blood flow at the ulcer base and ulcer margin. Further studies showed that cigarette smoke exposure alone did not cause any macroscopic injury in the stomach but significantly decreased the basal gastric blood flow in a concentration-dependent manner, which was coupled with an increase in mucosal xanthine oxidase (XO) activity. Pretreatment with allopurinol (Allo, 5 mg/kg, i.v.), a XO inhibitor, partially prevented the potentiating effect of cigarette smoke exposure on ulcer formation and also significantly improved the gastric blood flow. Ulcer induction itself dramatically increased constitutive nitric oxide synthase (cNOS) activity and prostaglandin E2 (PGE2) level in the gastric mucosa. However, the increment of cNOS activity but not PGE2 level was markedly attenuated by cigarette smoke exposure. Sodium nitroprusside (SNP, 25 or 50 microg/kg, i.v.), a nitric oxide (NO) donor, completely abolished the potentiating effect of cigarette smoke exposure on ulcer formation and also reversed the adverse effect on gastric blood flow. Thus, XO activation and cNOS reduction in the gastric mucosa are closely associated with the potentiating action of cigarette smoke exposure on ulcer formation in rats.
Ma
L
L
Department of Pharmacology, Faculty of Medicine, The University of Hong Kong, China.
Chow
J Y
JY
Cho
C H
CH
D019342:Acetic Acid / Q000633:toxicity*; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000096:biosynthesis; D004789:Enzyme Activation; D005753:Gastric Mucosa / Q000098:blood supply / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D010947:Plants, Toxic; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012906:Smoke / Q000009:adverse effects*; D013276:Stomach Ulcer / Q000139:chemically induced*; D014026:Nicotiana; D014969:Xanthine Oxidase / Q000378:metabolism
D012906:Smoke; D009599:Nitroprusside; D000493:Allopurinol; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D014969:Xanthine Oxidase; D015232:Dinoprostone; D019342:Acetic Acid