Na+/K+-ATPase activity in vascular smooth muscle from streptozotocin diabetic rat

Insulin-deficient diabetes impairs carbohydrate metabolism in a variety of tissues. Vascular smooth muscle may be susceptible to the diabetes-induced disturbance in glycolysis since Na+/K+-ATPase in this tissue preferentially utilizes ATP generated by glycolysis. The purpose of this study was to determine if chronic exposure to the metabolic alterations associated with insulin-deficient diabetes directly inhibited Na+/K+ ATPase activity, or its regulation, in vascular smooth muscle. Methods: Diabetes was induced by intravenous administration of streptozotocin (60 mg/kg). After 12 weeks, Na+/K+-ATPase activity in aorta and superior mesenteric artery was evaluated under a variety of conditions. Na+/K+ ATPase was estimated by measuring the influx of rubidium-86 (Rb-86) in the presence or absence of the Na+/K+-ATPase inhibitor, ouabain. The metabolism of [H-3]glucose and [C-14]glucose was used to estimate glycolysis or glucose oxidation, respectively. Results: Glycolysis and glucose oxidation were decreased in aortic smooth muscle (27 and 34%, respectively). An intact endothelium was associated with a marked decrease in ouabain-sensitive (pump-mediated) Rb-86 uptake in diabetic aorta. However, ouabain-sensitive Rb-86 uptake was similar in de-endothelialized aorta and superior mesenteric artery from diabetic and non-diabetic rats under both unstimulated conditions and during maximal stimulation. Removal of glucose or oxygen reduced ouabain-sensitive Rb-86 uptake to a similar extent in both groups. In contrast, the receptor-mediated stimulation of ouabain-sensitive Rb-86 uptake by insulin was decreased. Conclusions: These results suggest that intrinsic Na+/K+-ATPase activity is not diminished in diabetic vascular smooth muscle under physiological conditions and that the impairment of cellular metabolism in diabetic blood vessels does not limit stimulation of Na+/K+-ATPase activity. However, modulation of Na+/K+-ATPase activity by endothelial factors or insulin appears to be altered in aorta from diabetic rats.