Calcium metabolism in hypertension and allied metabolic disorders.
Data suggest a critical role for Ca metabolism in the pathophysiology of hypertensive disease. Intracellularly, all hypertension displays elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels. Extracellularly, however, heterogeneous defects in Ca and Mg metabolism are observed. This apparent divergence may be explained by considering all hypertension as the expression, in varying degrees, of two underlying Ca-related mechanisms: one (salt sensitive, low renin, Ca(2+)-antagonist sensitive) dependent on inappropriate cellular Ca2+ uptake from the extracellular space and the other (salt insensitive, renin dependent, Ca(2+)-antagonist insensitive) dependent on increased cellular Ca2+ release from intracellular sites. Recent work highlights the role of 1,25-dihydroxyvitamin D3 and the newly described parathyroid hypertensive factor in volume-dependent low-renin forms of hypertension. Altered cellular ion handling may also explain metabolic and clinical correlates of hypertension, e.g., peripheral insulin resistance, hyperinsulinemia, obesity, and non-insulin-dependent diabetes mellitus (NIDDM). Thus, all subjects with NIDDM, whether hypertensive or not, display the same elevated cytosolic free-Ca2+ and suppressed free-Mg2+ levels observed in hypertension. Furthermore, adiposity, the level of blood pressure, and fasting and postglucose hyperinsulinemia are all closely and quantitatively related to intracellular free-Ca2+, free-Mg2+, and pH levels. This suggests a broader hypothesis, in which hypertension, obesity, insulin resistance, and NIDDM, each usually considered a distinct clinical entity, represent different clinical expressions of a common defect in cellular ion handling, hence explaining their frequent clinical coexistence in the general population.
Resnick
L M
LM
Cardiovascular Center, New York Hospital - Cornell Medical Center, New York 10021.
D002116:Calcitonin / Q000097:blood; D002117:Calcitriol / Q000097:blood; D002118:Calcium / Q000378:metabolism*; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D007333:Insulin Resistance / Q000502:physiology; D008954:Models, Biological; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology*; D012016:Reference Values; D012083:Renin / Q000097:blood; D015290:Second Messenger Systems
D002116:Calcitonin; D012083:Renin; D002117:Calcitriol; D002118:Calcium