The role of dietary calcium in hypertension: a hierarchical overview

The role of calcium in clinical hypertension can be best understood by a hierarchical model in which the blood pressure effects of a dietary signal depend on alterations of hormonal systems specific for that signal. These alterations mediate both the cellular recognition of these signals as well as the resultant clinical responses to them. In the case of both dietary calcium and dietary salt, these systems appear to include calcium regulating hormones having direct, calcium-dependent vasoactive properties, and which are linked to the activity of the renin-angiotensin system. Altered salt and calcium intake exert reciprocal linked effects on these hormone systems and on blood pressure. These reflect altered cellular calcium uptake from the extracellular space, salt-induced calcium hormones stimulating and calcium-induced suppression of these hormones inhibiting extracellular calcium uptake. Among normotensive individuals, this is associated with a reciprocal calcium-dependent suppression or stimulation of renin secretion, respectively, resulting in an offsetting decreased or increased angiotensin II-mediated release of calcium into the cytoplasm from intracellular stores. Hence, no significant change in cytosolic free calcium or, consequently, in blood pressure usually results from increasing or decreasing dietary salt or calcium intake. However, whether due to genetic or other environmental factors as yet undefined, the metabolic "set point" of plasma renin activity in some subjects is already suppressed, or, alternatively, is unresponsive to the above hormonally mediated dietary mineral variations. Under these circumstances, increases in dietary salt will cause cytosolic free calcium and thus blood pressure to rise, whereas increased dietary calcium in these very same "salt-sensitive" subjects will offset the effect of salt, and lower pressure in these individuals. This analysis suggests that although increasing oral calcium intake to achieve at least current nutritional standards is entirely appropriate, uniform recommendations for all hypertensives to further increase or decrease dietary calcium or salt may be inappropriate and will obscure those for whom these maneuvers are particularly relevant.