ENDOTHELIUM-DEPENDENT INHIBITION OF NA+-K+ATPASE ACTIVITY IN RABBIT AORTA BY HYPERGLYCEMIA - POSSIBLE ROLE OF ENDOTHELIUM-DERIVED NITRIC-OXIDE

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) Rb-86-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 < 0.01). Similar decreases (45%; P < 0.01) in Na+-K+ ATPase activity were seen when rings incubated with 5.5 mM glucose were exposed to N(G)-monomethyl L-arginine (300-mu-M), 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 < 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.