pHi regulation in myocardium of the spontaneously hypertensive rat: Compensated enhanced activity of the Na+-H+ exchanger

Néstor G. Pérez, Bernardo V. Alvarez, María C. Camilión De Hurtado, Horacio E. Cingolani

Research output: Contribution to journalArticle

Abstract

To elucidate the mechanisms controlling pHi 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, was more alkaline in SHR (7.23±0.03) than in WKY rats (7.10±0.03) (Pi in the SHR (pHi 7.26±0.03 and 7.28±0.03 before and after SITS, respectively). (3) The fall in pH, 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, Pi 6.99, Pi 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 pHi 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, in the presence of HCO3--CO2 buffer in SHR (+0.08±0.02, Pi 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+ independent. (4) No difference in the rate of pHi 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 pHi suggests that an increased pHi 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 pHi 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
StatePublished - Dec 1995
Externally publishedYes

Fingerprint

Sodium-Hydrogen Antiporter
Inbred SHR Rats
Myocardium
Inbred WKY Rats
4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid
Anions
Buffers
Chloride-Bicarbonate Antiporters
Papillary Muscles
Ion Transport
Bicarbonates
Fluorescent Dyes

Keywords

  • BCECF
  • Myocardial pH
  • Na-H exchange
  • Na-independent Cl/HCO exchange
  • Spontaneously hypertensive rats

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Pérez, N. G., Alvarez, B. V., Camilión De Hurtado, M. C., & Cingolani, H. E. (1995). pHi regulation in myocardium of the spontaneously hypertensive rat: Compensated enhanced activity of the Na+-H+ exchanger. Circulation Research, 77(6), 1192-1200.

pHi regulation in myocardium of the spontaneously hypertensive rat : Compensated enhanced activity of the Na+-H+ exchanger. / Pérez, Néstor G.; Alvarez, Bernardo V.; Camilión De Hurtado, María C.; Cingolani, Horacio E.

In: Circulation Research, Vol. 77, No. 6, 12.1995, p. 1192-1200.

Research output: Contribution to journalArticle

Pérez, NG, Alvarez, BV, Camilión De Hurtado, MC & Cingolani, HE 1995, 'pHi regulation in myocardium of the spontaneously hypertensive rat: Compensated enhanced activity of the Na+-H+ exchanger', Circulation Research, vol. 77, no. 6, pp. 1192-1200.
Pérez, Néstor G. ; Alvarez, Bernardo V. ; Camilión De Hurtado, María C. ; Cingolani, Horacio E. / pHi regulation in myocardium of the spontaneously hypertensive rat : Compensated enhanced activity of the Na+-H+ exchanger. In: Circulation Research. 1995 ; Vol. 77, No. 6. pp. 1192-1200.
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T1 - pHi regulation in myocardium of the spontaneously hypertensive rat

T2 - Compensated enhanced activity of the Na+-H+ exchanger

AU - Pérez, Néstor G.

AU - Alvarez, Bernardo V.

AU - Camilión De Hurtado, María C.

AU - Cingolani, Horacio E.

PY - 1995/12

Y1 - 1995/12

N2 - To elucidate the mechanisms controlling pHi 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, was more alkaline in SHR (7.23±0.03) than in WKY rats (7.10±0.03) (Pi in the SHR (pHi 7.26±0.03 and 7.28±0.03 before and after SITS, respectively). (3) The fall in pH, 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, Pi 6.99, Pi 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 pHi 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, in the presence of HCO3--CO2 buffer in SHR (+0.08±0.02, Pi 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+ independent. (4) No difference in the rate of pHi 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 pHi suggests that an increased pHi 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 pHi induced by the antiport would not prevent an increase in intracellular Na+ mediated by the Na+-H+ exchanger.

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KW - Myocardial pH

KW - Na-H exchange

KW - Na-independent Cl/HCO exchange

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