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

The transgenic rat TGR(mREN2)27 is a new monogenetic model of hyperten sion. The mouse Ren-2 renin gene is integrated into their genome and t he 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 a nd from 8 normotensive Sprague-Dawley rats (SD). Na+!i was measured u sing the fluorescent dye sodium-binding benzofuran isophthalate in a f luorescence spectrophotometer at 500 nm emission with excitation wavel engths of 340 nm and 385 nm. Calibration of the fluorescence signal in terms of Na+!i was performed by calibration of fluorescent dye loade d lymphocytes in suspensions with known extracellular sodium concentra tion in the presence of ionophors to equilibrate extracellular and int racellular sodium concentration. Na+!i in resting lymphocytes was sig nificantly 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 inhibitio n of Na-K-ATPase by 0.5 mM ouabain for 5 minutes Na+!i was significan tly increased in lymphocytes from SD to 36.5 +/- 3.4 mM (p < 0.001 com pared 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 f rom TGR(mREN2)27 (35.4 +/- 0.6 mM). The present results suggest that r educed Na-K-ATPase activity in TGR(mREN2)27 producing increased restin g Na+!i is associated with hypertension.