pH(i) regulation in myocardium of the spontaneously hypertensive rat: Compensated enhanced activity of the Na+-H+ exchanger

N. G. Perez, B. V. Alvarez, M. C.C. De Hurtado, H. E. Cingolani

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1192-1200
Number of pages9
JournalCirculation research
Volume77
Issue number6
DOIs
StatePublished - Jan 1 1995

Keywords

  • BCECF
  • Na-H exchange
  • Na-independent Cl/HCO exchange
  • myocardial pH(i)
  • spontaneously hypertensive rats

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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