CELLULAR IONS IN HYPERTENSION, DIABETES, AND OBESITY - A NUCLEAR-MAGNETIC-RESONANCE SPECTROSCOPIC STUDY

To investigate the cellular basis linking hypertension, non-insulin-dependent diabetes mellitus (NIDDM), and obesity, we used P-31 and F-19 nuclear magnetic resonance spectroscopy to measure intracellular pH (pH(i)), free magnesium (Mg(i)), and cytosolic free calcium (Ca(i)) in erythrocytes of obese and NIDDM subjects with and without hypertension. Compared with normotensive, nondiabetic controls (Ca(i)), 25.2 +/- 1.4 nM; Mg(i), 232 +/- 8-mu-M), Ca(i) was elevated in both normotensive (36.8 +/- 2.7 nM, sig = 0.005) and hypertensive (43.4 +/- 2.9 nM, sig = 0.001) NIDDM subjects, and Mg(i) was concomitantly suppressed (normotensive: 206 +/- 11-mu-M, sig = 0.05; hypertensive: 196 +/- 8-mu-M, sig = 0.001). Similar but less striking changes were noted in obese subjects. Values of pH(i) were significantly lower (sig = 0.05) in all hypertensive groups compared with their normotensive controls. Continuous relations were observed for all subjects between Ca(i) and diastolic blood pressure (r = 0.649, p < 0.001) and body mass index (r = 0.564, p < 0.001), between Mg(i) and diastolic blood pressure (r = - 0.563, p < 0.001) and fasting blood glucose ( r = - 0.580, p < 0.001), and in diabetics, between pH(i) and diastolic blood pressure (r = - 0.680, p < 0.001). Thus, the constellation of elevated Ca(i) and suppressed Mg(i) and pH(i) levels is characteristic of the hypertensive state. These abnormalities of cellular ion handling in whole or in part common to hypertension, diabetes, and obesity may contribute to the pathophysiology of these syndromes and may help to explain their frequent clinical coexistence.