Mechanisms underlying stimulation of gastroduodenal HCO3- secretion by NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, in rats.
We investigated the mechanism underlying stimulation of HCO3- secretion by the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in the gastroduodenal mucosa of anesthetized rats. A chambered stomach (in the presence of omeprazole) or a duodenal loop was perfused with saline, and HCO3- secretion was measured at pH 7.0 by a pH-stat method. Intravenous administration of L-NAME increased gastroduodenal HCO3- secretion with a concomitant rise in arterial blood pressure and a decrease in heart rate, and the changes were all antagonized by simultaneous administration of L-arginine. Vagotomy had no effect on the increased blood pressure response, but significantly inhibited the decrease of heart rate and increase of HCO3- secretion caused by L-NAME. The HCO3- stimulatory action of L-NAME was also inhibited by prior administration of yohimbine or prazosin. These agents alone lowered blood pressure and reduced the magnitude of the blood pressure response caused by L-NAME, leading to inhibition of heart rate changes. When delta HCO3- output induced by L-NAME was plotted against delta blood pressure change (from basal values) under various conditions, a significant relationship was found between these two factors. These results suggest that L-NAME stimulates gastroduodenal HCO3- secretion in association with the inhibition of endogenous NO production, and this mechanism may be in part mediated by a neural reflex through the vagal efferent nerve, resulting from the pressor response to L-NAME.
Takeuchi
K
K
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan.
Takehara
K
K
Okabe
S
S
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001639:Bicarbonates / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004386:Duodenum / Q000187:drug effects* / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects* / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D007413:Intestinal Mucosa / Q000187:drug effects / Q000378:metabolism; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical; D015016:Yohimbine / Q000494:pharmacology
D001639:Bicarbonates; D015016:Yohimbine; D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin