McGrowder, Donovan A.; Ragoobirsingh, Dalip; Dasgupta,Tara P
Author Affiliation, Ana.
Department of Basic Medical Sciences
The hyperglycaemic effect of S-nitroso-glutathione in the dog
Journal of Nitric Oxide-biology and Chemistry
Date of Publication
The present study investigates the pharmacological activity of the nitric oxide (NO) donor S-nitrosoglutathione (GSNO) on the plasma glucose and insulin levels in healthy normoglycemic dogs. The plasma nitrate and nitrite concentrations were measured by a commercial autoanalyzer and taken as the biochemical markers of in vivo nitric oxide formation. Plasma glucose levels were measured by the oxidase method, while the insulin levels were determined by radioimmunoassay. The possible effect of the coadministration of ascorbic acid (vitamin C) and GSNO on plasma glucose levels was also examined. In healthy normoglycemic dogs, adminstration of 35 and 50 mg/kg of GSNO caused a dose-dependent increase in postprandial plasma glucose levels. The plasma glucose levels were significantly elevated at the 1.5-, and 2.5-h time interval of the oral glucose tolerance test at both concentrations of GSNO (P<0.05). These values were significantly higher than those obtained using captopril (control). Futhermore, coadministration of 35 mg/kg of GSNO and 50mg/kg ascorboc acid enhanced the postprandial hyperglycaemic effect observed for the administration of only 35 mg/kg of GSNO. There was a 35-100% increase n plasma nitrate concentration on adminstration of both doses of GSNO. Intravenous adminstration of GSNO (35 mg/kg) and captopril (20mg/kg) significantly decreased the mean arterial blood pressure and increased the heart rate. The blood pressure-lowering effect of these drugs was more pronounced on systolic than on diastolic blood pressure (p< 0.04). These results suggests that in healthy normoglycaemic dogs: (a) nitric oxide released from GSNO increases postprandial plasma glucose levels and inhibits glucose-stimulated insulin secretion, (b) ascorbic acid enhances the postprandial hyperglycaemic effect of GNSO, probably by increasing the release of NO, and (c) GSNO decreases mean arterial blood pressure and increase heart rate in normotensive dogs.....