Calcium Metabolism in Experimental Hypertension

Abstract

Conclusion

Clearly, Ca²⁺ metabolism is altered in hypertension at both the whole animal and cellular level. Furthermore, dietary Ca²⁺ deficiency is associated with human hypertension at the epidemiologic level and oral Ca²⁺ supplementation lowers blood pressure in human and experimental hypertension. In this review, we have presented the integrated view that a constellation of systemic abnormalities of Ca²⁺ metabolism in hypertension results in inefficient Ca²⁺ conservation and relative Ca²⁺ deficiency. Furthermore, the cellular findings in hypertension suggest increased cell membrane Ca²⁺ permeability and a compromised ability of the cell to remove or sequester intracellular Ca²⁺. Paradoxically this leads to increased intracellular free Ca²⁺ stores in the face of reduced extracellular Ca²⁺. Unfortunately most of the whole animal and cellular work has been carried out using different tissues. Nonetheless, it seems reasonable to hypothesize that abnormal Ca²⁺ handling at the cellular level is ultimately reflected at the organ and whole animal level so that alterations in vascular smooth muscle, intestine, kidney, erythrocytes, and so on are due to the same underlying defect manifested in many cell lines. The underlying defect may involve the cell membrane Ca²⁺-ATPase (68), an intrinsic membrane binding protein (114), a cell membrane Ca²⁺ channel, or perhaps some other process.

If an underlying cellular defect in Ca²⁺ metabolism exists in some forms of hypertension, then what is the link with elevated blood pressure? While altered Ca²⁺ metabolism in hypertension may be an epiphenomenon of some other metabolic process that is primarily responsible for the elevated blood pressure, a more central role for altered Ca²⁺ metabolism in hypertension is suggested by the myriad of defects that have been reported. However, the issue will remain unsettled until the underlying bases for disrupted calcium and vascular homeostasis in hypertension are found. Understanding of calcium metabolism and blood pressure regulation in hypertension, whether as shared or separate mechanisms, should prove to be a challenging but productive area of future research.