Na-dependent changes in intracellular Ca in spontaneously hypertensive rat hearts

To determine whether Na/Ca exchange is altered in primary hypertension, Na-dependent changes in intracellular Ca, ([Ca](i)), were measured in isolated perfused hearts from Wistar-Kyoto (WKY) and spontaneously hypertensive (SHR) rats. Intracellular Na, (Na(i), mEq/kg dry wt), and [Ca](i) were measured by NMR spectroscopy. Control [Ca](i) was less in WKY than SHR (176 ± 18 vs 253 ± 21 nmol/l; mean ± S.E., P < 0.05), whereas Na(i) was not significantly different. One explanation for this is that net Na/Ca exchange flux is decreased in SHR. If this hypothesis is correct, the rate of Ca uptake in SHR should be less than WKY when Na/Ca exchange is reversed by decreasing the transmembrane Na gradient. The Na gradient was reduced by decreasing extracellular Na, ([Na](o)) and/or by increasing [Na](i). To increase [Na](i), Na uptake was stimulated by acidification while Na extrusion by Na/K ATPase was inhibited by K-free perfusion. Seventeen minutes after acidification, Na(i) had increased but was not significantly different in SHR and WKY (18.0 ± 2.3 to 57.4 ± 7.6 vs 20.3 ± 0.6 to 66.5 ± 4.8 mEq/kg dry wt, respectively). Yet [Ca](i) was greater in WKY than SHR (1768 ± 142 vs 1201 ±90 nmol/l; P < 0.05). [Ca](i) was also measured after decreasing [Na](o) from 141 to 30 mmol/l. Fifteen minutes after reducing [Na](o), [Ca](i) was greater in WKY than SHR (833 ± 119 vs 425 ± 94 nmol/l; P < 0.05). Thus for both protocols, decreasing the transmembrane Na gradient led to increased [Ca](i) in both SHR and WKY, but less increase in SHR. The results are consistent with the hypothesis that Na/Ca exchange activity is less in SHR than WKY myocardium.