This supplemental application requests support for the completion of a nutritional study of the effects and interactions of dietary calcium and sodium in patients with essential hypertension. The underlying hypothesis of this study is that dietary calcium supplementation can lower blood pressure in essential hypertension. While there is epidemiologic data suggesting that the level of calcium intake can influence blood pressure, this data and its interpretation are controversial. In addition, the extent of the effect of calcium (if present) and its mechanism(s) are uncertain. It has been suggested that the variability in the available data may be due to differential effects of dietary manipulation in subsets of the hypertensive population. Because it was clear that more information was needed before general dietary recommendations were considered, proposals addressing these issues were invited and the current study funded. These ongoing investigations are based on the careful characterization of mild-to-moderate essential hypertensives as to salt-sensitivity and renin status. Methods include determination of systolic and diastolic blood pressure, supine and upright (random-zero technique), studies of electrolyte and fluid balance, assessment of forearm vascular reactivity to adrenergic agonists, studies of platelet function and intracellular electrolytes. Circulating calcium and sodium levels, renin, aldosterone, catecholamines, parathyroid hormone and 1,25(OH)2-vitamin D3 levels and calcium excretion are assessed. Patients are randomized to precisely- controlled constant diets, providing from 400 to 2000 mg calcium and from 10 to 300 mEq sodium/day for eight weeks, utilizing a 3 x 3 factorial design with repeated measures. The dietary content of potassium, chloride and magnesium are also controlled. Repeated determination of baseline measures are performed at four and eight weeks to define both the extent and time course of these effects and to provide insight into their potential mechanisms.
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