Metabolic considerations and cellular mechanism related to calcium's antihypertensive effects.

Whether maintenance of normal calcium homeostasis can afford protection against the development of hypertension in humans has emerged as a controversial area of both clinical and basic cardiovascular disease research. The data that have provoked this debate are derived from epidemiological reports, human studies, animal investigations, and cellular research. Ten published reports have identified an association between greater dietary calcium consumption and lower blood pressure in humans. In both humans and experimental animals with hypertension, several end-organ defects have been identified that are consistent with an inability to maintain external calcium balance. With the provision of supplemental dietary calcium, both humans and experimental models with high blood pressure have reduced their blood pressure. A variety of membrane-associated defects of Ca2+-ATPase-dependent calcium transport have been identified in cells derived from multiple organs of both the hypertensive animal and human. These abnormalities of cellular calcium handling could account for the failure of the hypertensive subject to appropriately defend its calcium balance. More important, they provide a theoretical mechanism by which calcium, interacting with calmodulin, might favorably modify vascular smooth muscle function and, thereby, peripheral vascular resistance.