Dietary calcium modulates renal BBM angiotensin II binding and Na⁺-H⁺ antiporter activity in SHR

Dietary Ca is an important modulator of blood pressure in the spontaneously hypertensive rat (SHR). Since the kidney plays a key role in the pathogenesis of hypertension, the purpose of this study was to determine the potential renal mechanisms of the blood pressure-lowering effect of increasing dietary Ca content. In 21-day-old SHR fed 0.1 vs. 3.6% Ca diet for 14 days, increasing dietary Ca had no significant effects on basal [704 ±50 in 0.1% Ca vs. 784 ±61 ng angiotensin I (ANG I)·mg^-1·h^-1 in 3.6% Ca, P = not significant (NS)], isoproterenol-stimulated (1,057 ± 52 in 0.1% Ca vs. 1,104 ±59 ng ANG I·mg^-1·h^-1 in 3.6% Ca, P = NS), or angiotensin II (ANG II)-inhibited (370 ±50 in 0.1% Ca vs. 411 ±39 ng ANG I·mg^-1·^-1 in 3.6% Ca, P = NS) renal superficial cortical slice renin release. In contrast, in apical brush-border membrane (BBM) vesicles isolated from the superficial cortex, increasing dietary Ca caused a significant decrease in ANG II binding, which was mediated by a decrease in the number of binding sites (B_max, 376 ±14 in 0.1% Ca vs. 234 ±6 fmol ANG II/mg BBM protein in 3.6% Ca, P < 0.01), and no change in the affinity [dissociation constant (K_d), 17.8 ± 1.4 in 0.1% Ca vs. 13.4 ±2.8 nM ANG II in 3.6% Ca, P = NS]. In addition, increasing dietary Ca caused a significant decrease in BBM vesicle Na⁺-H⁺ antiport, which was mediated by a decrease in the maximal activity (V_max) (13.53 ±0.17 in 0.1% Ca vs. 11.35 ±0.21 nmol Na·5 s^-1·mg BBM protein^-1 in 3.6% Ca, P < 0.05) and no change in the affinity [Michaelis constant (K_m), 8.65 ±0.41 in 0.1% Ca vs. 8.64 ±0.35 mM Na in 3.6% Ca, P = NS]. Our study therefore indicates that increasing dietary Ca causes decreases in renal BBM ANG II binding sites and Na⁺-H⁺ antiport activity without changing intrarenal renin secretion. These intrarenal effects of dietary Ca on ANG II binding and Na⁺-H⁺ antiport may be important mechanisms of the blood pressure-modulating effect of dietary Ca in the SHR.