Dietary calcium and blood pressure in experimental models of hypertension. A review

More than 80 studies have reported lowered blood pressure after dietary calcium enrichment in experimental models of hypertension. The evidence presented here suggests that dietary calcium may act concurrently through a number of physiological mechanisms to influence blood pressure. The importance of any given mechanism may vary depending on the experimental model under consideration. Supplemental dietary calcium is associated with reduced membrane permeability, increased Ca(2+)-ATPase and Na,K-ATPase, and reduced intracellular calcium. These results suggest that supplemental calcium may limit calcium influx into the cell and improve the ability of the VSMC to extrude calcium. This could be a direct effect of calcium on the VSMC or an indirect effect mediated hormonally. The calcium-regulating hormones have all been found to have vasoactive properties and therefore may influence blood pressure. Furthermore, CGRP and the proposed parathyroid hypertensive factor are both vasoactive substances that are responsive to dietary calcium. Therefore, diet-induced variations in calcium-regulating hormones may influence blood pressure. Modulation of the sympathetic nervous system is another important way that dietary calcium can influence blood pressure. There is evidence of altered norepinephrine levels in the hypothalamus as a consequence of manipulations of dietary calcium as well as changes in central sympathetic nervous system outflow. Dietary calcium has also been shown to specifically modify alpha 1-adrenergic receptor activity in the periphery. In some experimental models of hypertension, dietary calcium may alter blood pressure by changing the metabolism of other electrolytes. For example, the ability of calcium to prevent sodium chloride-induced elevations in blood pressure may be attributed to natriuresis. However, natriuresis does not account for all of the interactive effects of calcium and sodium chloride on blood pressure. Sodium chloride-induced hypertension may be due in part to calcium wasting and subsequent elevation of calcium-regulating hormones. Chloride is an important mediator of this effect because it appears that sodium does not cause calcium wasting when it is not combined with chloride. More attention to the central nervous system effects of dietary calcium is needed. Not only can calcium itself influence neural function, but many of the calcium-regulating hormones appear to affect the central nervous system. The influence of calcium and calcium-regulating hormones on central nervous system activity may have important implications for blood pressure regulation and also may extend to other aspects of physiology and behavior.