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) (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 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, P<.05). (4) The velocity of pH, 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 pH, 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.
Original language | English (US) |
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Pages (from-to) | 1192-1200 |
Number of pages | 9 |
Journal | Circulation research |
Volume | 77 |
Issue number | 6 |
State | Published - Dec 1995 |
Externally published | Yes |
Keywords
- BCECF
- Myocardial pH
- Na-H exchange
- Na-independent Cl/HCO exchange
- Spontaneously hypertensive rats
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Physiology