Calciotropic hormones in salt-sensitive essential hypertension: 1,25-dihydroxyvitamin D and parathyroid hypertensive factor

Abstract

Hypothesis: Some, but not all, men and women display a pressor response to increases in dietary salt intake. The mechanism(s) underlying this salt-sensitive hypertension remains poorly defined. We have developed a hypothesis that all hypertension arises from an imbalance between mechanisms of cytosolic calcium accumulation from the extracellular space versus calcium release into the cytoplasm from intracellular storage sites. Extracellular calcium-dependent hypertension predominates in salt-sensitive subjects, while excess angiotensin II mediates the excess intracellular calcium release that is characteristic of renin-dependent salt-insensitive forms of hypertension. Studies on pressor hormones: We investigated potential etiologic factors mediating the cellular calcium accumulation in salt-sensitive hypertensive human subjects, and focused on two calcium-related circulating hormonal substances, 1,25-dihydroxyvitamin D and the recently described parathyroid hypertensive factor. Both of these substances directly facilitate calcium transport from the extracellular space in the cell. Furthermore, levels of these hormones are greatest in black normotensive and low-renin essential hypertensive subjects, both groups associated with salt-related hypertensive disease. Lastly, dietary salt loading elevates 1,25-dihydroxyvitamin D and parathyroid hypertensive factor levels, and the greater the level of either hormone, the greater the pressor response to salt.

Conclusions: It is reasonable to consider that these salt-induced cellular ionophoric actions of 1,25-dihydroxyvitamin D and parathyroid hypertensive factor contribute, at least in part, to the mechanism of salt-sensitive hypertension in man.