Functional alterations of cardiac (Na,K)-ATPase in L-NAME induced hypertension

(Na,K)-ATPase, an enzyme involved in the active translocation of Na+ and K+ ions across cell membranes was shown to be affected by nitric oxide (NO) in various tissues. In the present study the functional alterations of (Na,K)-ATPase after chronic inhibition of nitric oxide synthesis were studied in rat hearts. Four weeks lasting administration of an L-arginine analogue, the N(G)-nitro-L-arginine methyl ester (L-NAME) induced an increase in the systolic blood pressure of about 36%. In this hypertension the kinetic parameters Km and Vmax for ATP-activation of the (Na,K)-ATPase did not show any significant changes. Activation of the enzyme by its cofactor Na+ revealed no change in the Vmax, but the K(Na) increased by 50%. Two weeks after terminating the administration of L-NAME the blood pressure returned to control values. In these conditions the activity of (Na,K)-ATPase increased, due to enlarged affinity of the ATP-binding site as revealed from the diminished Km value for ATP. The K(Na) value for activation with Na+ returned to control value. Our findings indicate that there is no change in energy utilization by the (Na,K)-ATPase during L-NAME induced hypertension in the heart. The transport properties of the enzyme are deteriorated, due to its decreased sensitivity to Na+. This inhibition of the (Na,K)-ATPase might be responsible for the increase of [Na+]i during lowered NO synthesis. In hearts from rats that recovered from the hypertension, the (Na,K)-ATPase increases its activity due to improved ATP binding properties.