Cytosolic pH in cultured cardiac myocytes and fibroblasts from newborn spontaneously hypertensive rats.
Newborn spontaneously hypertensive rats (SHR) develop cardiac hypertrophy before a rise in blood pressure. Cytosolic pH (pHi) has been discovered to modulate cell growth and proliferation; therefore, we have investigated pHi in myocytes and fibroblasts from 3- to 4-day-old SHR and normotensive Wistar (W) and Wistar-Kyoto controls (WKY). The ratio of heart to body weight was higher in SHR than in W and WKY (7.56 +/- 0.10 v 6.21 +/- 0.10 and 5.98 +/- 0.14 mg/g in 10, 5, and 7 groups of 20 to 40 animals; P less than .001 for both). Cytosolic pH, determined with the fluorescent probe BCECF, was measured from the sixth to the eighth day in culture on confluent cells. The mean pHi was higher in myocytes from SHR than in those from W or WKY rats (7.19 +/- 0.03, N = 30, v 7.09 +/- 0.03 and 7.11 +/- 0.02, N = 25 and 30; P = .008 and .024, respectively). In contrast, pHi was similar in fibroblasts from the three strains (7.21 +/- 0.03, 7.18 +/- 0.03, and 7.19 +/- 0.02, N = 15, 15, and 14, in SHR, W, and WKY rats, respectively). External acidification induced similar decreases in pHi from SHR and WKY myocytes, maintaining higher pHi values in SHR myocytes along the entire external pH (pHo) range studied. The inhibition of Na+/H+ exchange by the amiloride derivative, ethylisopropylamiloride, decreased the steady-state pHi of myocytes independently of the initial pHi values. This study demonstrated a cytosolic alkalinization in contractile cardiac cells from SHR before a significant rise in blood pressure and in the absence of hemodynamic influences and specific plasma factors.(ABSTRACT TRUNCATED AT 250 WORDS)
Astarie
C
C
Department of Pharmacology, Necker Medical School, Paris, France.
David-Dufilho
M
M
Millanvoye-Van Brussel
E
E
Freyss-Béguin
M
M
Devynck
M A
MA
D000818:Animals; D006332:Cardiomegaly / Q000503:physiopathology; D002478:Cells, Cultured; D003593:Cytoplasm / Q000502:physiology; D005347:Fibroblasts / Q000502:physiology*; D006321:Heart / Q000502:physiology*; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D009200:Myocardial Contraction; D009206:Myocardium / Q000166:cytology*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY