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Calcium metabolism in hypertension and allied metabolic disorders
1Cardiovascular Center, New York Hospital - Cornell Medical Center, New York 10021.
Insights
Hypertension involves abnormal calcium (Ca2+) and magnesium (Mg2+) metabolism. These ion imbalances may also link to obesity, insulin resistance, and diabetes, suggesting a common cellular defect.
Area of Science:
- Cardiovascular Physiology
- Cellular Metabolism
- Endocrinology
Background:
- Hypertension is linked to calcium (Ca) metabolism, with intracellular elevations in free Ca2+ and suppressed free Mg2+ observed.
- Extracellular Ca and Mg metabolism show varied defects across hypertension types.
- Two primary Ca-related mechanisms may underlie hypertension: cellular Ca2+ uptake and intracellular Ca2+ release.
Purpose of the Study:
- To explore the role of Ca and Mg metabolism in hypertension pathophysiology.
- To investigate the link between altered cellular ion handling and metabolic comorbidities.
- To propose a unifying hypothesis for the coexistence of hypertension, obesity, insulin resistance, and NIDDM.
Main Methods:
- Analysis of intracellular and extracellular Ca and Mg metabolism in hypertensive patients.
- Review of recent findings on vitamin D and parathyroid hypertensive factor in low-renin hypertension.
- Correlation analysis of intracellular ion levels with metabolic parameters like insulin resistance and obesity.
Main Results:
- All hypertensive patients exhibit elevated cytosolic free Ca2+ and suppressed free Mg2+.
- Two distinct Ca-related mechanisms contribute to hypertension: cellular uptake and intracellular release.
- Non-insulin-dependent diabetes mellitus (NIDDM) patients share similar intracellular ion profiles with hypertensive individuals.
- Adiposity, blood pressure, and hyperinsulinemia correlate with intracellular Ca2+, Mg2+, and pH.
Conclusions:
- Hypertension pathophysiology is critically linked to Ca and Mg metabolism defects.
- Altered cellular ion handling may explain the co-occurrence of hypertension, obesity, insulin resistance, and NIDDM.
- These conditions may represent different clinical manifestations of a common cellular ion handling defect.
Abstract:
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.