© 1995 American Heart Association, Inc.
Articles |
pHi Regulation in Myocardium of the Spontaneously Hypertensive Rat
Compensated Enhanced Activity of the Na+-H+ Exchanger
From Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata (Argentina).
Correspondence to Dr Horacio E. Cingolani, Centro de Investigaciones Cardiovasculares, Facultad de Ciencias Médicas, Universidad Nacional de La Plata, Calle 60 y 120, 1900 La Plata, Argentina.
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 pHi 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 pHi in the SHR (pHi 7.26±0.03 and 7.28±0.03 before and after SITS, respectively). (3) The fall in pHi 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 pHi 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 pHi 6.99, P<.05). (5) After EIPA inhibition, the rate of pHi 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 pHi 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 pHi 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 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.
Key Words: myocardial pHi • Na+-H+ exchange • Na+-independent Cl-/HCO3- exchange • spontaneously hypertensive rats • BCECF
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