title: Failure of the nitric oxide synthase inhibitor to stimulate duodenal bicarbonate secretion in streptozotocin-diabetic rats.
abstract: We examined the HCO(3)- stimulatory effects of L-NAME (N(G)-nitro-L-arginine methyl ester) in the proximal duodenum of streptozotocin (STZ)-induced diabetic rats and compared with those of 16,16-dimethyl prostaglandin E2 (dmPGE2) and vagal electrical stimulation. Male SD rats were given STZ (70 mg/kg) i.p., and the experiments were done using 1 approximately 6 week STZ-diabetic rats with blood glucose levels of >300 mg/dl. Under urethane anesthesia the HCO(3)- secretion was measured in the proximal duodenal loop using a pH-stat method and by adding 10 mM HCl. Hyperglycemic conditions appeared 1 week after STZ treatment and remained during 6 week-test period. The duodenal HCO(3)- secretory response to L-NAME was significantly decreased in STZ-diabetic rats; the degree of reduction was dependent on the duration of diabetes, and the stimulatory effect disappeared completely in rats after 5 approximately 6 weeks of diabetes. Intravenous administration of L-NAME markedly increased arterial blood pressure with significant decrease in heart rate in normal rats, whereas in STZ-diabetic rats this agent caused only pressor response without any effect on heart rate. STZ-diabetic rats also secreted significantly less amount of HCO(3)- from the duodenum in response to dmPGE2 and vagal electrical stimulation after 5 approximately 6 weeks of diabetes. These all changes observed in STZ-diabetic rats were significantly reversed by daily injection of insulin. These results suggest that 1) L-NAME failed to stimulate duodenal HCO(3)- secretion in STZ-diabetic rats, and 2) impairment of the duodenal HCO(3)- secretory ability in STZ-diabetic conditions is due to both vagal-dependent neuronal dysfunction and decreased sensitivity of the secreting cell.
authors.affiliation: Department of Pharmacology & Experimental Therapeutics, Kyoto Pharmaceutical University, Misasagi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Takehara
authors.forename: K
authors.initials: K
authors.lastname: Tashima
authors.forename: S
authors.initials: S
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Takeuchi
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000818:Animals; D000897:Anti-Ulcer Agents / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014630:Vagus Nerve / Q000502:physiology
chemical_list: D000897:Anti-Ulcer Agents; D001639:Bicarbonates; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D019001:Nitric Oxide Synthase; D015064:16,16-Dimethylprostaglandin E2; D019331:NG-Nitroarginine Methyl Ester