The current study tested the hypothesis that dietary Ca2+supplementation reverses the NaCl-sensitive component of hypertension and the associated neu-rochemical abnormalities in the NaCl-sensitive spontaneously hypertensive rat (SHR-S). Male SHR-S were begun on one of four diets at 8 weeks of age: control (0.75% NaCl/0.68% Ca2+); high NaCl (8.00% NaCl/0.68% Ca2+); high Ca2+(0.75% NaCl/2.00% Ca2+); and high NaCl/high Ca2+(8.00% NaCl/2.00% Ca2+). High NaCl SHR-S (−2 weeks) had higher mean arterial pressure (MAP) (161 ± 4 mm Hg) than controls (149 ± 3 mm Hg; P <.05). Supplementation with Ca2+prevented the rise in MAP in high NaCl rats, but did not alter MAP in controls. The 8% NaCl diet elevated plasma norepi-nephrine and reduced anterior hypothalamic (AHA) norepinephrine stores and turnover; concomitant Ca2+supplementation restored both plasma norepinephrine and AHA norepinephrine turnover to normal. Clonidine was microinjected into the AHA of rats maintained on the four diets for 2 weeks to test the hypothesis that dietary Ca2+supplementation prevents the previously observed NaCl-in-duced upregulation of ±2-adrenoceptors in AHA. Clonidine caused dose-dependent decreases in MAP that were greater in high NaCl rats than in controls. The Ca2+supplementation prevented the exaggerated depressor response to clonidine in the high NaCl group, but not in the controls. The Ca2+supplementation had no effect on pretreatment MAP or on MAP responses to clonidine in control NaCl-resistant SHR (SHR-R) or Wistar-Kyoto (WKY) rats. Thus, dietary Ca2+supplementation prevents the NaCl-induced exacerbation of hypertension and augmented depressor response to clonidine in SHR-S by increasing noradrenergic input to AHA, thereby preventing the upregulation of AHA α2-adrenoceptors. © 1990 by the American Journal of Hypertension, Ltd.
