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) 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.
Gupta
S
S
Diabetes and Metabolism Unit, Boston University School of Medicine, Massachusetts 02118.
Sussman
I
I
McArthur
C S
CS
Tornheim
K
K
Cohen
R A
RA
Ruderman
N B
NB
D000818:Animals; D001011:Aorta / Q000201:enzymology*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology; D004730:Endothelium, Vascular / Q000502:physiology*; D006943:Hyperglycemia / Q000201:enzymology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009994:Osmolar Concentration; D011817:Rabbits; D012414:Rubidium Radioisotopes / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis / Q000037:antagonists & inhibitors*; D019323:omega-N-Methylarginine
D012414:Rubidium Radioisotopes; D009599:Nitroprusside; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D001120:Arginine; D000254:Sodium-Potassium-Exchanging ATPase