Insulin does not regulate vascular smooth muscle Na+, K(+)-ATPase activity in rabbit aorta.
To determine whether insulin regulates vascular smooth muscle Na+, K(+)-ATPase activity and if impaired insulin stimulation of vascular smooth muscle Na+, K(+)-ATPase activity could be a cause of increased vascular reactivity to norepinephrine and angiotensin II in diabetic states, the effects of insulin on Na+, K(+)-ATPase activity were examined in normal rabbit aortic intima-media incubated with normal plasma glucose and myo-inositol levels for 30 min. Insulin at 100 microU/ml (600 pmol/l) had no effect on Na+, K(+)-ATPase activity. At 250 microU/ml it caused a 4.2 +/- 0.8% increase, and at 500 microU/ml insulin caused a 17.7 +/- 1.4% increase in Na+, K(+)-ATPase activity that was completely inhibited by amiloride (1 mmol/l). Human insulin-like growth factor I (600 pmol/l) caused an 18.0 +/- 1.0% increase in Na+, K(+)-ATPase activity that was inhibited by amiloride. Insulin does not regulate (stimulate) aortic vascular smooth muscle Na+, K(+)-ATPase activity. Supraphysiological insulin concentrations, probably acting through an insulin-like growth factor I receptor, stimulate Na+/H+ exchange in aortic vascular smooth muscle and cause small secondary increases in Na+, K(+)-ATPase activity. In aortic intima-media incubated with normal plasma glucose and myo-inositol levels, endogenously released adenosine stimulates and maintains a component of resting Na+, K(+)-ATPase activity and stimulates acute increases in activity when norepinephrine (1 mumol/l) or angiotensin II (100 nmol/l) is added. These adenosine-stimulated components of Na+, K(+)-ATPase activity are selectively inhibited when the medium glucose is raised to 30 mmol/l during a 30-min equilibration and 30-min incubation.(ABSTRACT TRUNCATED AT 250 WORDS)
Cox Institute, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia.
D A
DA
Simmons
A I
AI
Winegrad
D000584:Amiloride / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001012:Aorta, Abdominal / Q000201:enzymology*; D007328:Insulin / Q000494:pharmacology*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000201:enzymology*; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D012413:Rubidium / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D007328:Insulin; D000804:Angiotensin II; D007334:Insulin-Like Growth Factor I; D000584:Amiloride; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium; D011188:Potassium; D009638:Norepinephrine