Our previous studies demonstrated that (a) dietary Ca2+ supplementation prevents the rise in blood pressure, activation of sympathetic outflow, and reductions in anterior hypothalamic norepinephrine (NE) content and release induced in NaCl-sensitive spontaneous hypertensive rats (SHR-S) by dietary NaCl loading; and (b) stimulation of α2-adrenoceptors by microinjection of clonidine into the anterior hypothalamic area (AHA) results in an exaggerated depressor response in SHR-S fed a high NaCl diet as compared with SHR-S on a basal diet. The current study tested the hypothesis that dietary Ca2+ supplementation prevents these NaCl induced defects in AHA noradrenergic neurons. SHR-S were placed on diets containing: (a) high NaCl; (b) high Ca2+; (c) high Ca2+, high NaCl; or (d) basal NaCl, basal Ca2+ (control). Two weeks later, clonidine (0.6, 1.2, or 2.5 μg) was microinjected into the AHA of conscious rats. Clonidine caused dose-dependent decreases in mean arterial pressure (MAP) and heart rate (HR) that were greater in SHR-S on the high NaCl diet than on the control diet. Ca2+ supplementation prevented the exaggerated depressor response to clonidine in high NaCl-fed SHR-S, but did not reduce the response in SHR-S on the basal NaCl diet. Ca2+ supplementation had no effect on blood pressure (BP) or HR responses to clonidine in control NaCl-resistant SHR (SHR-R) or in normotensive Wistar Kyoto (WKY) rats. The results support the hypothesis that dietary Ca2+ supplementation prevents exacerbation of hypertension and augmented depressor response to clonidine in NaCl-loaded SHR-S by increasing noradrenergic input to AHA, thereby preventing the upregulation of AHA α2 adrenoceptors usually seen in high NaCl-fed SHR-S.