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

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 mumol/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 < 0.05). (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).