[ROLES OF CONSTITUTIVE SYNTHASES OF NITRIC OXIDE IN THE REGULATION OF GASTRIC BICARBONATE SECRETION INDUCED BY MILD IRRITATION OF THE MUCOSA].
Roles of isoforms of constitutive synthase of nitric oxide, neuronal or endothelial (nNOS or eNOS), in control of gastric bicarbonate secretion induced by mild irritation of the gastric mucosa was assessed at the normoacid state or after blockade of gastric acid secretion with omeprazole. In anesthetized rats, the concentration of HCO3- in luminal perfusate was calculated basing on measurements of pH/PCO2. Mucosal irritation during 20 min with acidic hypertonic solution (1 M NaCl, pH 2.0) caused marked and omeprazole-independent increase of HCO-secretion. Selective blocker ofnNOS in vivo 7-nitroindazole (7-NI), and the nonselective blocker ofnNOS and eNOS, N(G)-nitro-L-arginine (L-NNA), were applied either intravenously (10 mg/kg), or locally via retrograde injection into the splenic artery (1 mg/kg). At the normo-acid state, the irritation-induced secretion of was suppressed by 7-NI, but was not affected by L-NNA. After administration of omeprazole, both 7-NI and L-NNA equally inhibited HCO3- output. The effect of 7-NI (but not L-NNA) was abolished by cyclooxygenase (COX) inhibitor, indomethacin, which by itself suppressed irritation-induced secretion of HCO3-. Additionally, bicarbonate output was substantially reduced by the blocker of soluble guanylate cyclase (GC), methylene blue. We conclude that irritation-induced secretion of HCO3- is largely mediated by intramural nNOS and depends on GC-COX interaction. As it was theoretically estimated, eNOS activity caused a reduction of HCO3- output in the normo-acid stomach. Omeprazole abolished the effect of eNOS.
V A
VA
Zolotarev
Yu V
YV
Andreeva
E A
EA
Vershinina
R P
RP
Kropycheva
D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005753:Gastric Mucosa / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007191:Indazoles / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007509:Irritants / Q000494:pharmacology*; D008297:Male; D052248:Nitric Oxide Synthase Type I / Q000037:antagonists & inhibitors / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology; D009853:Omeprazole / Q000494:pharmacology; D017207:Rats, Sprague-Dawley
D001639:Bicarbonates; D004791:Enzyme Inhibitors; D007191:Indazoles; D007509:Irritants; D019335:Nitroarginine; D052248:Nitric Oxide Synthase Type I; D052250:Nitric Oxide Synthase Type III; C496322:Nos1 protein, rat; C496316:Nos3 protein, rat; D009853:Omeprazole; C080122:7-nitroindazole; D007213:Indomethacin