INCREASED CYTOSOLIC SODIUM AND REDUCED NA,K-ATPASE ACTIVITY IN TRANSGENIC RATS

The transgenic rat TGR(mRen2)27 is a new monogenetic model in hyperten sion research that develops fulminant hypertension after the mouse Ren -2(d) renin gene has been integrated into its genome. To evaluate the molecular mechanism of development of hypertension in this animal mode l, we measured cytosolic free sodium concentration in intact lymphocyt es from seven transgenic rats and eight age-matched normotensive Sprag ue-Dawley rats using the novel sodium-sensitive fluorescent dye sodium -binding benzofuran-isophthalate. Resting cytosolic sodium was signifi cantly higher in transgenic rats compared with Sprague-Dawley rats (31 .7+/-2.2 versus 18.2+/-0.4 mmol/L, mean+/-SEM, P<.001). Inhibition of Na,K-ATPase by 0.5 mmol/L ouabain for 5 minutes significantly increase d lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5+/-3.4 mm ol/L (P<.001 compared with resting value), whereas no significant chan ge could be observed in transgenic rats (35.4+/-0.6 mmol/L), indicatin g that Na,K-ATPase is less responsive in transgenic rats. The Na,K-ATP ase activity from erythrocytes was measured with an enzyme-linked assa y. Na,K-ATPase activity was significantly reduced in transgenic rats c ompared with Sprague-Dawley rats (4.0+/-0.3 versus 8.1+/-0.6 U/L, P<.0 01). We concluded that reduced Na,K-ATPase activity leads to elevated cytosolic sodium in this model of genetic hypertension.