Vanadate effect on the Na,K-ATPase and the Na-K pump in in vitro-grown rat vascular smooth muscle cells.
The impact of vanadate on the Na,K-ATPase system in the vascular smooth muscle cell is poorly understood. The present study describes the kinetics of the effect of vanadate on Na,K-ATPase and the Na-K pump in in vitro grown rat VSMC's. Vanadate interaction with the Na,K-ATPase system in vascular smooth muscle cells was examined by observing its influence on ouabain-sensitive adenosine triphosphate hydrolysis in disrupted cells rendered permeable by osmotic shock, and the uptake of rubidium by intact cells. The I50 for vanadate inhibition of ouabain-sensitive hydrolysis of adenosine triphosphate occurred at vanadate concentrations of 10(-6) to 10(-7) M. This inhibition was potassium dependent. The maximal inhibitory effect of vanadate occurred at potassium concentrations of 10-20 mEq/liter. Sodium exerted a moderate antagonistic influence on vanadate inhibition of ouabain-sensitive adenosine triphosphate hydrolysis. Rubidium uptake by vascular smooth muscle cells was not altered within 120 minutes when 10(-5) M vanadate was added to the medium containing intact vascular smooth muscle cells. Yet, vanadium concentrations in the vascular smooth muscle cells within this incubation period reached levels 1.48-fold higher than the extracellular vanadate concentrations of 10(-5) M. These observations indicate that vanadate is a potent inhibitor of the VSMC Na,K-ATPase in disrupted vascular smooth muscle cells. However, in intact vascular smooth muscle cells vanadium gaining access into the vascular smooth muscle cell's interior does not inhibit the Na-K pump, probably because of its binding to intracellular proteins and/or conversion from the vanadate to the vanadyl ion.
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014638:Vanadates; D014639:Vanadium / Q000494:pharmacology*
D014639:Vanadium; D014638:Vanadates; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium