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, (Nai, 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 Nai 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, Nai 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.
Anderson
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Department of Human Physiology, University of California, Davis 95616-8644, USA. seanderson@ucdavis.edu
Gray
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Atherley
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R
Cala
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PM
D000255:Adenosine Triphosphate / Q000378:metabolism; D000643:Ammonium Chloride; D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D005461:Fluorine; D006863:Hydrogen-Ion Concentration; D006973:Hypertension / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism*; D009924:Organ Culture Techniques; D010759:Phosphorus Isotopes; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012964:Sodium / Q000378:metabolism*; D012975:Sodium Isotopes; D019831:Sodium-Calcium Exchanger / Q000378:metabolism; D013816:Thermodynamics
D010759:Phosphorus Isotopes; D012975:Sodium Isotopes; D019831:Sodium-Calcium Exchanger; D000643:Ammonium Chloride; D005461:Fluorine; D000255:Adenosine Triphosphate; D012964:Sodium; D008274:Magnesium; D002118:Calcium