NA+ K+-ATPASE ACTIVITY IN VASCULAR SMOOTH-MUSCLE FROM STREPTOZOTOCIN-DIABETIC RAT/

Insulin-deficient diabetes impairs carbohydrate metabolism in a variet y of tissues. Vascular smooth muscle may be susceptible to the diabete s-induced disturbance in glycolysis since Na+/K+-ATPase in this tissue preferentially utilizes ATP generated by glycolysis. The purpose of t his study was to determine if chronic exposure to the metabolic altera tions associated with insulin-deficient diabetes directly inhibited Na +/K+ ATPase activity, or its regulation, in vascular smooth muscle. Me thods: Diabetes was induced by intravenous administration of streptozo tocin (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, ouab ain. The metabolism of [H-3]glucose and [C-14]glucose was used to esti mate glycolysis or glucose oxidation, respectively. Results: Glycolysi s and glucose oxidation were decreased in aortic smooth muscle (27 and 34%, respectively). An intact endothelium was associated with a marke d decrease in ouabain-sensitive (pump-mediated) Rb-86 uptake in diabet ic aorta. However, ouabain-sensitive Rb-86 uptake was similar in de-en dothelialized aorta and superior mesenteric artery from diabetic and n on-diabetic rats under both unstimulated conditions and during maximal stimulation. Removal of glucose or oxygen reduced ouabain-sensitive R b-86 uptake to a similar extent in both groups. In contrast, the recep tor-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 me tabolism in diabetic blood vessels does not limit stimulation of Na+/K +-ATPase activity. However, modulation of Na+/K+-ATPase activity by en dothelial factors or insulin appears to be altered in aorta from diabe tic rats.