To elucidate the mechanisms controlling pH(i) in myocardium of the spontaneously hypertensive rat (SHR), experiments were performed in papillary muscles (isometrically contracting at 0.2 Hz from SHR and age-matched normotensive Wistar-Kyoto (WKY) rats loaded with the pH-sensitive fluorescent probe BCECF-AM. An enhanced activity of the Na+-H+ exchanger was detected in the hypertrophic myocardium of SHR. This conclusion was based on the following: (1) The myocardial pH(i) was more alkaline in SHR (7.23 ± 0.03) than in WKY rats (7.10 ± 0.03) (P<.05) in HEPES buffer, (2) SITS (0.1 mmol/L in HEPES buffer) did not alter pH(i) in the SHR (pH(i) 7.26 ± 0.03 and 7.28 ± 0.03 before and after SITS, respectively. (3) The fall in pH(i) observed after 20 minutes of Na+-H+ exchanger inhibition [5 μmol/L 5-(N-ethyl-N- isopropyl)amiloride (EIPA)] was greater in SHR (-0.16 ± 0.01) than in WKY rats (-0.09 ± 0.02, P<.05. (4) The velocity of pH(i) recovery from an intracellular acid load was faster in SHR than in WKY rats (0.068 ± 0.02 versus 0.014 ± 0.002 pH units/min at pH(i) 6.99, P<.05). (5) After EIPA inhibition, the rate of pH(i) recovery from the same acid load decreased to a similar value in both rat strains (0.0032 ± 0.002 pH units/min in SHR and 0.0032 ± 0.002 pH units/min in WKY rats). Under the more physiological HCO3-CO2 buffer, no significant difference in steady state myocardial pH(i) was detected between rat strains (7.15 ± 0.03 in SHR and 7.11 ± 0.05 in WKY rats). This finding suggested that an acidifying bicarbonate-dependent mechanism was fully compensating for the hyperactivity of the Na+-H+ exchanger in SHR. The following pieces of evidence support an enhanced activity of the Na+-independent Cl-HCO3 exchanger as the mechanism accounting for the compensation: (1) SITS (0.1 mmol/L) increased steady state pH(i) in the presence of HCO3-CO2 buffer in SHR (+0.08 ± 0.02, P<.05) but not in WKY rats (+0.04 ± 0.04). (2) The rate of pH(i) recovery from an alkaline load was faster in SHR than in WKY rats (0.075 ± 0.028 versus 0.027 ± 0.016 pH units per minute, respectively; P<.05. (3) The enhanced recovery from an alkaline load in the SHR was Na+ independent. (4) No difference in the rate of pH(i) recovery was detected between SHR and WKY rats when the alkaline load was performed after SITS blockade. Comparison of net HCO3 efflux at a given pH(i) suggests that an increased pH(i) is not the cause of the hyperactivity of the anion exchanger. Since this anion exchanger is not driving Na+, the offset of the increase in pH(i) induced by the antiport would not prevent an increase in intracellular Na+ mediated by the Na+-H+ exchanger.
- Na-H exchange
- Na-independent Cl/HCO exchange
- myocardial pH(i)
- spontaneously hypertensive rats
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine