Endothelium-dependent inhibition of Na+-K+ ATPase activity in rabbit aorta by hyperglycemia : possible role of endothelium-derived nitric oxide

• Published in: The Journal of clinical investigation 1992-09, Vol.90 (3), p.727-732
• Main Authors: GUPTA, S, SUSSMAN, I, MCARTHUR, C. S, TORNHEIM, K, COHEN, R. A, RUDERMAN, N. B
• Format: Article
• Language: English
• Subjects: Animals; Aorta - enzymology; Arginine - analogs & derivatives; Arginine - pharmacology; Biological and medical sciences; Diabetes Mellitus, Experimental - enzymology; Endocrinopathies; Endothelium, Vascular - physiology; Hyperglycemia - enzymology; Male; Medical sciences; Nitric Oxide - metabolism; Nitroprusside - pharmacology; omega-N-Methylarginine; Osmolar Concentration; Rabbits; Rubidium Radioisotopes - metabolism; Sodium-Potassium-Exchanging ATPase - analysis; Sodium-Potassium-Exchanging ATPase - antagonists & inhibitors
• ISSN: 0021-9738; 1558-8238
• DOI: 10.1172/jci115944

Hyperglycemia has been shown to diminish Na(+)-K+ ATPase activity in rabbit aorta. To examine the basis for this effect, aortic rings were incubated for 3 h in Krebs-Henseleit solution containing 5.5 or 44 mM glucose, and Na(+)-K+ ATPase activity was then quantified on the basis of ouabain-sensitive (OS) 86Rb-uptake. Incubation with 44 mM glucose medium caused a 60% decrease in Na(+)-K+ ATPase activity in rings with intact endothelium (from 0.22 +/- 0.01 to 0.091 +/- 0.006 nmol/min per mg dry wt; P less than 0.01). Similar decreases (45%; P less than 0.01) in Na(+)-K+ ATPase activity were seen when rings incubated with 5.5 mM glucose were exposed to NG-monomethyl L-arginine (300 microM), an inhibitor of endothelium-derived nitric oxide (EDNO) synthesis or when the endothelium was removed (43% decrease). The decrease in Na(+)-K+ ATPase activity induced by hyperglycemia was totally reversed upon adding to the medium either L-arginine, a precursor of EDNO biosynthesis or sodium nitroprusside, which bypasses endothelium and directly activates the soluble guanylate cyclase in vascular smooth muscle. A decrease in Na(+)-K+ ATPase activity (42%; P less than 0.05), only seen in the presence of endothelium, was also observed in aortas taken directly from alloxan-induced diabetic rabbits. These studies suggest that the decrease in vascular Na(+)-K+ ATPase activity induced by hyperglycemia is related, at least in part, to a decrease in the basal release of EDNO. They also suggest that alterations in basal EDNO release and possibly Na(+)-K+ ATPase activity contribute to the impairment in vascular relaxation caused by hyperglycemia and diabetes.