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 (Vmax), and the Michaelis constant (Km), 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, Vmax was higher in transgenic rats, as revealed by 2-way ANOVA (F (1, 80) = 39.06, p < 0.0001). Following ACF, Vmax remained unchanged in both control and transgenic rats. In contrary, ACF had opposing effects on Km 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 Vmax) was detected in the kidney of TGR(mREN2)27 rats. Although the creation of ACF did not alter the Vmax 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.

Institute for Clinical and Experimental Medicine Centre for Experimental Medicine Prague Czech Republic

Institute for Heart Research Centre of Experimental Medicine Slovak Academy of Sciences Bratislava Slovak Republic

Institute of Physiology Faculty of Medicine Comenius University in Bratislava Bratislava Slovakia

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