Na+/K(+)-ATPase activity in vascular smooth muscle from streptozotocin diabetic rat.
OBJECTIVE
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 (86Rb) in the presence or absence of the Na+/K(+)-ATPase inhibitor, ouabain. The metabolism of [3H]glucose and [14C]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) 86Rb uptake in diabetic aorta. However, ouabain-sensitive 86Rb 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 86Rb uptake to a similar extent in both groups. In contrast, the receptor-mediated stimulation of ouabain-sensitive 86Rb 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.
Smith
J M
JM
Department of Physiology, Midwestern University, Downers Grove, IL 60515, USA.
Paulson
D J
DJ
Solar
S M
SM
D000818:Animals; D001011:Aorta; D046508:Culture Techniques; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology* / Q000378:metabolism; D002149:Energy Intake; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis; D008297:Male; D017538:Mesenteric Artery, Superior; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010084:Oxidation-Reduction; D051381:Rats; D017207:Rats, Sprague-Dawley; D012414:Rubidium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism*
D012414:Rubidium Radioisotopes; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose