Effects of lead and natriuretic hormone on kinetics of sodium-potassium-activated adenosine triphosphatase: possible relevance to hypertension.
Inhibition of vascular smooth muscle sodium-potassium-activated adenosine triphosphatase (Na-K-ATPase) has been postulated as a central mechanism in enhancing vascular contractility. In the present study, kinetics of inhibition of Na-K-ATPase by lead, ouabain, and natriuretic hormone (NH) was studied in a purified hog cerebral cortex enzyme preparation. Determination of I50 values for lead, ouabain, and NH revealed that NH is the most potent inhibitor of the enzyme system (0.8 x 10(-6) M ouabain equivalents). Kinetic analyses indicated that lead and NH exhibited different inhibitory mechanisms. The inhibition by lead was noncompetitive with respect to potassium and competitive with respect to sodium and MgATP. Natriuretic hormone was noncompetitive with respect to potassium, uncompetitive with respect to MgATP, and exhibited no inhibitory effect with respect to sodium. Synergism between lead and NH in the inhibition of Na-K-ATPase raises the possibility that lead may be a contributory factor in hypertension via this mechanism.
Weiler
E
E
Division of Nephrology/Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA.
Khalil-Manesh
F
F
Gonick
H
H
D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology*; D006973:Hypertension / Q000201:enzymology / Q000209:etiology; D066298:In Vitro Techniques; D007854:Lead / Q000494:pharmacology*; D045283:Natriuretic Agents / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013552:Swine
D045283:Natriuretic Agents; D007854:Lead; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase