Alterations in renal Na,K-ATPase activity and protein expression in rat models of pressure and volume overload

Purpose: To explore an unexamined mechanism of cardiorenal pathophysiology by assessing renal Na, K-ATPase kinetics in rat models of pressure overload, volume overload, and their combination. Methods: Two rat models with differing renin-angiotensin-aldosterone system activity were used: control Hannover Sprague Dawley (HAN) rats and transgenic TGR(mREN2)27 rats, the later modeling pressure overload. Each model included sham and aortocaval fistula (ACF)-operated groups to induce volume overload. The kinetic parameters of Na,K-ATPase were determined: maximal velocity of enzyme reaction (V-max), and the Michaelis constant (K-m), representing the ATP concentration at half-maximal velocity and reflecting the enzyme's affinity for ATP. Results: Histological studies, along with assessment of selected markers of renal injury and remodeling, confirmed kidney tissue alterations in both TGR(mREN2)27 rats and animals subjected to ACF-surgery. Regarding Na,K-ATPase, V-max was higher in transgenic rats, as revealed by 2-way ANOVA (F ((1, 80)) = 39.06, p < 0.0001). Following ACF, V-max remained unchanged in both control and transgenic rats. In contrary, ACF had opposing effects on K-m in the two rat models: it decreased in HAN rats , but increased in TGR(mREN2)27 rats after surgery. Conclusion: With regard to functional properties of the Na, K-ATPase, an increased number of substrate molecules converted to products per active site per unit time (indicated by V-max) was detected in the kidney of TGR(mREN2)27 rats. Although the creation of ACF did not alter the V-max parameter, a notable impairment in the enzyme's ability to bind ATP substrate within physiologically relevant concentrations was observed in TGR(mREN2)27 rats, but not in HAN rats.