Is calcium more important than sodium in the pathogenesis of essential hypertension?

Abstract

SUMMARY The hypothesis that abnormalities of calcium homeostasis at both an organ and cellular level are a primary factor in the pathogenesis of human and experimental hypertension forms the basis of this review. The rapidly expanding data base relating disordered calcium metabolism to altered vascular smooth muscle function and increased peripheral vascular resistance is summarized and integrated with the observations that reduced dietary calcium intake is the most consistent nutritional correlate of hypertension in the United States. The role of sodium and sodium chloride in pathogenesis of hypertension is reassessed in the light of new data from epidemiological clinical research, experimental models, and cell physiology investigations. The data supporting the thesis that the effects of sodium or chloride or both on blood pressure may represent, in selected situations, secondary influences mediated through induced changes in calcium homeostasis are presented. The interface between these nutritional factors and the normal regulation of vascular smooth muscle is discussed, providing a theoretical framework in which to assess the current information and to formulate the necessary future research. (Hypertension 7: 607-627, 1985) KEY WORDS • calcium • sodium • vascular smooth muscle cells • spontaneously hypertensive rats • deoxycorticosterone acetate rat • calmodulin • Ca -activated adenosine triphosphatase * nutrition F EW concepts in medicine are more widely accepted than the theoretical link between dietary sodium and the pathogenesis of essential hypertension.l-) In spite of this perceived consensus, however, many investigators have remained skeptical of the notion that sodium or a defect in sodium balance, or both, is the principal cause of high blood pressure in most humans with essential hypertension.

Vitamin D3 and cardiovascular function in rats.

“…Because only total CPK was measured in the present study, it cannot be said for certain whether the increase in serum CPK in the vitamin D3-deficient rats is due to damage to myocardial or skeletal muscle or both. As (38), and a correlation between increased BP and hypocalcemia has been demonstrated in patients and animal models of hypertension (34). In addition, the possibility exists that vitamin D3 may play a role in the changes in cardiovascular function that can accompany diabetes (39), lengthy bedrest or immobilization (40, 41), or prolonged periods of weightlessness (41), because circulating levels of 1,25(OH)2D3 are reduced by these conditions (42)(43)(44)(45).…”

“…(26,27). Administration of either 25(OH)D3 (28) or l-a-hydroxyvitamin D3 (27) (34). Administration of Ca to young spontaneously hypertensive rats has also been shown to attenuate the development of hypertension in these animals (35), and will reverse "fixed" hypertension in adult animals (36 (37).…”

Blood pressure development of the spontaneously hypertensive rat after concurrent manipulations of dietary Ca2+ and Na+. Relation to intestinal Ca2+ fluxes.

“…A variety of abnormalities of cellular Ca2+ metabolism have been identified in the SHR (5,(8)(9)(10)(11)(12)(13)(14)(15)(16). In vascular tissue, these have included an increased membrane permeability (8,10), decreased vesicular uptake of Ca2+ (12,13), and reduced Ca2' ATPase activity (12,13), defects consistent with a primary failure ofCa2+ calmodulin activation ( 11) of membrane stabilization and Ca2+ sequestration in contractile tissue.…”

Dietary alcohol, calcium, and potassium. Independent and combined effects on blood pressure.

“…9 Although the influence of potassium on blood pressure has not been investigated as thoroughly as that of sodium, it has been evaluated in some epidemiologic6'9,10 and experimental1"",2 studies.…”