Evidence for the role of PO4 deficiency in antihypertensive action of a high-Ca diet

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Abstract
Previous studies indicated a salutary effect of a high-Ca diet on high blood pressure (BP). The mechanism, however, is obscure. With balance and clearance techniques, the role of parathyroid hormone (PTH), volume contraction, hypercalcemia and PO4 deficiency was evaluated in female spontaneous hypertensive rats (SHR). The antihypertensive effects of a high (4.3%) Ca diet in intact animals (groups I and II) could be reproduced in both 9- and 22-wk-old chronic stable parathyroidectomized (PTX) rats (groups III and IV), when compared with a low (0.22%) or normal (1.2%) Ca diet. In both short (7 days) and long (12 wk) term exposure to the high-Ca diet, evidence for volume contraction could not be documented despite hypercalcemia sustained through the 12th wk (10.8 vs. 9.7 mg/100 ml, group I control, P < 0.02). When produced by i.p. injections, chronic hypercalcemia of similar magnitudes as oral Ca supplements failed to reduce BP in either intact (group VI) or PTX (group IV) rats. Rats in group IV fed the high-Ca diet displayed marked hypophosphatemia (3.2 vs. 6.9 mg/100 ml), hypophosphaturia (0.15 vs. 15 mg/day), hypermagnesiuria (11 vs. 7.7 mg/day) and drastically reduced net intestinal PO4 absorption (13.3 .+-. 7.5 vs. 66.8 .+-. 7.5 mg/day) compared with rats fed 1.2% Ca diet. To test the PO4-deficiency hypothesis, additional SHR (group V) were fed either 1.2% Ca diet and injected i.p. with NaCl or fed 4.3% Ca diet, with half of these animals injected with neutral NaPO4 and half with NaCl. While the high-Ca diet reduced BP in rats allowed to become PO4 deficient (167 .+-. 3 vs. 181 .+-. 4 Torr), it did not correct the hypertension (191 .+-. 2 Torr) in rats receiving PO4 replacement. Subsequent PO4 repletion in rats fed the high-Ca diet also prevented the antihypertensive action (196 .+-. 4 vs. 200 .+-. 2 Torr). The antihypertensive effects of a high-Ca diet are apparently mediated by PO4 deficiency and the mechanism is independent of PTH, hypercalcemia and volume contraction.