Sensitivity to the pressor effect, of dietary NaCI and the depressor effect, of dietary Ca is inherited. High NaCl diets accelerate the development and or exacerbate the severity of hypertension in NaCl-sensitive substrains of spontaneously hypertensive rat (SHR-S) but not in NaCl-resistant substrains of SHR (SHR-R) or in normotensive Wistar-Kyoto (WKY) control rats. High NaCl intake leads to increased circulating noradenaline levels and increased depressor responses to ganglionie blockade in SHR-S but not in SHR-R or WKY rats, indicating that peripheral sympathetic nervous system activity and neurogenic peripheral vascular tone are increased by NaCl supplementation in SHR-S. but not in SHR-R or WKY rats. Further. dietary NaCl loading in SHR-S decreases endogenous noradrenaline stores and noradrenaline release in the anterior hypothalamus, a brain region that contains neurons that give rise to depressor responses when stimulated chemically or electrically. These findings are consistent with the hypothesis that decreased activity of noradrenergic depressor neurons in the anterior hypothalamus mediate and increase in blood pressure that occurs in NaCI-sensitine animals during dietary NaCl supplementation by releasing tonic inhibition of sympathetic outflow. The exacerbation of hypertension and changes in central noradrenergic activity are observed only in NaCl-loaded SHR-S. not in SHR-R or WKY rats. indicating that these NaCl-induced alterations in central noradrenergic activity are genetically mediated. Dietary Ca supplementation prevents for reversest the NaCl-induced changes in blood pressure. peripheral sympathetic nervous system activity, and anterior hypothalamic noradrenaline release in SHR-S. suggesting that dietary NaCI and Ca may have opposing effects on the same regulators pathway. The genetic defect in NaCl Ca2+ sensitivity of blood pressure is not yet identified. but probably involve cation transport at the cellular level. © 1988 Raven Press, Ltd., New York.