PH(I) REGULATION IN MYOCARDIUM OF THE SPONTANEOUSLY HYPERTENSIVE RAT - COMPENSATED ENHANCED ACTIVITY OF THE NA+-H+ EXCHANGER

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 fit) from SHR and age-matched normotensive Wistar-Kyoto (WKY) rats loaded with the pi-I-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: (2) 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, in the SHR (pH(i) 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 mu mol/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 pi-Ii 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, 6.99, P<.05). (5) After EIPA inhibition, the rate of pi-Ii 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.