Calcium and hypertension

Abstract

Calcium plays a central role in regulation of the contractile properties of muscle, peripheral vascular tone and blood pressure. Since elevated peripheral resistance is the hallmark of hypertension, it follows that aberrations of calcium metabolism at either the cellular or systemic level may be involved in the pathogenesis of hypertension. A considerable body of evidence suggests a relationship between abnormalities of calcium metabolism and hypertension. This possibility is evident in the majority of the observational and clinical studies that have found an inverse relationship between blood pressure and dietary calcium intake. In essential hypertension there is evidence for an array of alterations of the calcium (Ca²⁺) regulatory system including increased cell calcium concentration [Ca²⁺]_i, increased Ca²⁺ uptake and decreased removal of [Ca²⁺]_i. Antihypertensive therapy has been reported to reduce [Ca²⁺]_i. A relationship between [Ca²⁺]_i and blood pressure is evident in both hypertensive and normotensive subjects. The calcium metabolism aberrations are present not only in hypertension per se, but to a greater or lesser extent in other cardiovascular and metabolic aspects of what has been termed "metabolic syndrome X", including obesity, insulin resistance, hyperinsulinemia, type 2 diabetes mellitus, an left ventricular hypertrophy. On the ground of it an ionic hypothesis of cardiovasular and metabolic disease has been formulated, in which the predisposition to, and/or the presence of hypertension, together with any or all of its allied syndromes referred to above all derive from an underlying Ca²⁺ metabolism defect, characterized in part by [Ca²⁺]_i. According to the ionic hypothesis, this abnormal intracellular ion environment, although common to all forms of hypertensive disease, reflects different mechanisms in different individuals. In salt-sensitive, low renin forms of hypertension, excess [Ca²⁺]_i derives from calcium-hormone-mediated, cellular calcium uptake from the extracellular space. Conversely, in salt-insensitive, renin-dependenthypertension, the same excess [Ca²⁺]_i derives instead from angiotensin II-mediated release of calcium into the cytosol from intracellular stores. All hypertension is then a combination, to varying degree, of these two general calcium-related mechanisms.