MULTINUCLEAR NMR-STUDIES OF INTRACELLULAR CATIONS IN THE PREHYPERTENSIVE RAT-KIDNEY

We previously reported a significant derangement of intracellular free calcium ion concentration in the isolated perfused kidney of adult spontaneously hypertensive rat (SHR) (J. Biol. Chem. 267, 3637-3643, 1992). In order to investigate whether an abnormality in intracellular free calcium or another ion precedes the development of elevated blood pressure in SHR, we have now compared intracellular free Ca2+, Na+ and pH, using P-31, F-19, and triple quantum-filtered (TQ) Na-23 NMR, in perfused kidneys from prehypertensive young SHR and normotensive young Wistar-Kyoto (WKY) rats (5-6 weeks old) which showed no significant difference in blood pressure (B.P. = 120 +/- 5 mmHg and 115 +/- 3 mmHg, for SHR and WKY rats, respectively). Like the adult kidney, no significant differences in intracellular ATP concentration or intracellular pH were found between young prehypertensive SHR and normotensive WKY rat kidneys. The TQ Na-23 NMR signal was 47% higher in the SHR kidney, but, due to biological variability and measurement errors, this difference could not be shown to be statistically significant. However, a significant (40%; P < 0.05) increase was found in O-2 consumption rate, a measure of the Na+/K+-ATPase activity, of the young prehypertensive SHR kidney in comparison to the age-matched WKY rat kidney (7.25 +/- 0.75 for SHR vs. 5.17 +/- 0.18 mu mol O-2/min g for WKY rat, n = 6). Furthermore, a highly significant (92%; P < 0.02) increase in intracellular free Ca2+ concentration was observed in kidneys from young SHR that had not yet developed high blood pressure in comparison to the kidneys from young normotensive WKY rats (648 +/- 76 nM vs. 339 +/- 39 nM, n = 4), despite the fact that there was no significant difference in blood pressure. Increased intracellular free Ca2+ thus appears to be part of a primary defect, in the prehyperten- sive young SHR kidney, which may, by way of increased release of arachidonic acid, and subsequent increased production of vasoconstricting arachidonic acid metabolites via the cytochrome P450 pathway, induce elevated blood pressure in the adult SHR.