Increased cytosolic sodium and reduced Na,K-ATPase activity in transgenic rats.
The transgenic rat TGR(mRen2)27 is a new monogenetic model in hypertension research that develops fulminant hypertension after the mouse Ren-2d renin gene has been integrated into its genome. To evaluate the molecular mechanism of development of hypertension in this animal model, we measured cytosolic free sodium concentration in intact lymphocytes from seven transgenic rats and eight age-matched normotensive Sprague-Dawley rats using the novel sodium-sensitive fluorescent dye sodium-binding benzofuranisophthalate. Resting cytosolic sodium was significantly 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 increased lymphocytic cytosolic sodium in Sprague-Dawley rats to 36.5 +/- 3.4 mmol/L (P < .001 compared with resting value), whereas no significant change could be observed in transgenic rats (35.4 +/- 0.6 mmol/L), indicating that Na,K-ATPase is less responsive in transgenic rats. The Na,K-ATPase activity from erythrocytes was measured with an enzyme-linked assay. Na,K-ATPase activity was significantly reduced in transgenic rats compared with Sprague-Dawley rats (4.0 +/- 0.3 versus 8.1 +/- 0.6 U/L, P < .001). We concluded that reduced Na,K-ATPase activity leads to elevated cytosolic sodium in this model of genetic hypertension.
Tepel
M
M
Medizinische Universitäts-Poliklinik, University of Münster, Germany.
Theilmeier
G
G
Bachmann
J
J
Barenbrock
M
M
Spieker
C
C
Ganten
D
D
Rahn
K H
KH
Zidek
W
W
D000818:Animals; D030801:Animals, Genetically Modified; D002478:Cells, Cultured; D003600:Cytosol / Q000378:metabolism; D004195:Disease Models, Animal; D006973:Hypertension / Q000097:blood* / Q000235:genetics / Q000503:physiopathology; D007700:Kinetics; D008214:Lymphocytes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D051379:Mice; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics*; D012964:Sodium / Q000097:blood*; D000254:Sodium-Potassium-Exchanging ATPase / Q000097:blood*; D013050:Spectrometry, Fluorescence; D013997:Time Factors
D010042:Ouabain; D012964:Sodium; D012083:Renin; D000254:Sodium-Potassium-Exchanging ATPase