Renal sodium pump regulation in deoxycorticosterone salt hypertension in the rat

The renal sodium pump participates in sodium homeostasis and has been predicted to have a role in salt dependent forms of hypertension. However, the status of the renal sodium pump in volume-dependent hypertension is unclear. We assessed the renal sodium pump and its activity in the deoxycorticosterone acetate (DOCA)-salt model in rats, a model of volume-dependent hypertension. Sprague-Dawley rats on ad libitum diet were compared with four groups of litter mates receiving high or low salt diets, with or without DOCA administration. The renal sodium pump evaluation included measurement of hydrolytic activity, ouabain binding capacity and affinity, sodium activation, active pump units (determined by phosphoenzyme level), dephosphorylation rate, and isoform specific molecular expression. Intrinsic enzyme properties, including sodium and ouabain affinities, as well as turnover rate per sodium pump, were identical among the five groups. In contrast, the combination of DOCA and high salt intake (DOCA high salt) produced marked, significant increases in hydrolytic activity, ouabain binding capacity, phosphoenzyme level, and alpha1-isoform expression. DOCA low salt animals showed much smaller but significant increases in pump number. We conclude that DOCA and volume expansion may each alter renal sodium pump regulation, but volume expansion is clearly dominant. Increased renal sodium pump activity in DOCA high salt animals would, if unmitigated, favor sodium reabsorption and may contribute to hypertension.