The nature and role of disturbances in calcium metabolism in genetic hypertension.

Abnormalities in Ca metabolism in genetic hypertension have been suggested by studies of the spontaneously hypertensive rat and of humans with essential hypertension. A state of relative Ca deficiency in genetic hypertension was previously hypothesized to explain the reduced serum ionized Ca, increased serum parathyroid hormone levels, and the association between oral Ca loading and mild reduction in blood pressure. Renal Ca leak, reduced intestinal Ca absorption, and diminished Ca intake were further postulated to account for the Ca deficient state. This hypothesis, however, is not supported by the following lines of evidence in genetic hypertension: the absence of fasting hypercalciuria owing to intrinsic tubular defects, increased net Ca absorption in vivo despite greater Ca retention before and during established hypertension, increased intracellular free Ca concentrations, the failure to aggravate the hypertension by 50% reduction in dietary Ca intake, and the failure to ameliorate the hypertension by maneuvers that augment Ca balance (parenteral Ca administration, a high Mg diet, and 1,25-dihydroxyvitamin D3 injections). The available literature may be explained by the alternative hypothesis that genetic hypertension is characterized by generalized membrane defects in Ca regulation, resulting in a relative increase in cytosolic free Ca. The mechanism (or mechanisms) and physiological consequences of the disturbances in Ca homeostasis, however, remain to be defined.