INCREASED INTRACELLULAR SODIUM CONCENTRATION AND IMPAIRED SODIUM-TRANSPORT SYSTEMS IN TRANSGENIC RATS TGR(MREN2)27

The transgenic rat TGR(mREN2)27 is a new monogenetic model of hypertension. The mouse Ren-2 renin gene is integrated into their genome and the rats are characterized by fulminant hypertension. Since changes of intracellular electrolyte content may be associated with hypertension, in the present study cytosolic free sodium concentration ([Na+]i) was investigated in intact lymphocytes from 7 hypertensive TGR(mREN2)27 and from 8 normotensive Sprague-Dawley rats (SD). [Na+]i was measured using the fluorescent dye sodium-binding benzofuran isophthalate in a fluorescence spectrophotometer at 500 nm emission with excitation wavelengths of 340 nm and 385 nm. Calibration of the fluorescence signal in terms of [Na+]i was performed by calibration of fluorescent dye loaded lymphocytes in suspensions with known extracellular sodium concentration in the presence of ionophors to equilibrate extracellular and intracellular sodium concentration. [Na+]i in resting lymphocytes was significantly higher in lymphocytes from TGR(mREN2)27 compared to SD (31.7 +/- 2.2 mM vs 18.2 0.4 mM, mean +/- SEM, p < 0.001). After inhibition of Na-K-ATPase by 0.5 mM ouabain for 5 minutes [Na+]i was significantly increased in lymphocytes from SD to 36.5 +/- 3.4 mM (p < 0.001 compared to resting value). On the other hand, inhibition of Na-K-ATPase by 0.5 mM ouabain did not significantly change [Na+]i in lymphocytes from TGR(mREN2)27 (35.4 +/- 0.6 mM). The present results suggest that reduced Na-K-ATPase activity in TGR(mREN2)27 producing increased resting [Na+]i is associated with hypertension.