To investigate the ionic actions of insulin in hypertension, 19 F-and 31 P-nuclear magnetic resonance spectroscopy were used to measure cytosolic free calcium (Ca i ) and intracellular free magnesium (Mg i ) levels in red blood cells from normal (n ϭ 9) and hypertensive (n ϭ 9) subjects before and 30, 60, 120, and 180 min after in vitro incubation with insulin. In hypertensive patients, basal Ca i levels were significantly higher (30.0 Ϯ 2.2 vs. 19.8 Ϯ 2.5 nmol/L; P Ͻ 0.05), and basal Mg i levels were significantly lower (170 Ϯ 10.9 vs. 209 Ϯ 8 mol/L; P Ͻ 0.05) than in normotensive subjects. In normal cells, insulin significantly elevated Ca i to 39.8 Ϯ 8.0, 50.1 Ϯ 8.2, 69.3 Ϯ 11.1, and 50.9 Ϯ 13.4 nmol/L at 30, 60, 120, and 180 min and Mg i to 238 Ϯ 10 264 Ϯ 14, 226 Ϯ 11, and 216 Ϯ 10 mol/L at 30, 60, 120, and 180 min. In hypertensive subjects, the insulin-dependent Ca i elevation was blunted, and Mg i accumulation was completely suppressed. Continuous relationships were observed between basal values of each ion and insulin responses; the greater the Ca i , the less the Ca i rose (r ϭ Ϫ0.574; P ϭ 0.013), and the lower the Mg i , the less Mg i rose (r ϭ 0.524; P ϭ 0.025). Furthermore, a blunting of Mg i responses to insulin could be reproduced in normal cells that were magnesium depleted by prior treatment either with A23187 in a calcium-free medium or with high glucose concentrations (15 mmol/L). Once again, insulin responsiveness followed basal Mg i levels (r ϭ 0.637; P Ͻ 0.001).Together, these data demonstrate ionic aspects of insulin resistance in hypertension and suggest that Ca i and Mg i levels may regulate cellular responsiveness to insulin. This may help to explain the different vascular actions attributed to insulin in normal compared with insulin-resistant states such as hypertension. (J Clin Endocrinol Metab 82: 1761-1765, 1997) I NSULIN resistance is often present in subjects with hypertension, obesity, and noninsulin-dependent diabetes mellitus (NIDDM); may be quantitatively related to peripheral vascular resistance and blood pressure (1-3); and is normally defined and measured in terms of altered indices of peripheral glucose utilization (4, 5). However, the mechanism(s) by which vascular consequences might ensue from this defect in glucose metabolism remains unclear, and we have sought to explain these relationships by investigating the potential role of altered steady state intracellular ion concentrations (6). We observed that in essential hypertensive (EH), obese, and/or diabetic subjects, the extent of cardiac hypertrophy, elevated blood pressure, and hyperinsulinemic responses to glucose loading are all closely related to altered steady state intracellular free magnesium (Mg i ), free calcium (Ca i ), and pH (7-9) levels.Furthermore, insulin itself has primary direct cellular ionic actions, independent of glucose, to increase Ca i and Mg i in peripheral red blood cells, platelets, and vascular smooth muscle cells (10 -12). As increasing Ca i might promote vasoconstriction, whereas st...
Objective To propose, in cases with coiling of the ovarian vessels, a classification of severity of torsion based on
Abstract-Preeclampsia is a pregnancy disorder of unknown origin, characterized by vasospasm, elevated blood pressure, and increased neuromuscular irritability, features common to syndromes of magnesium deficiency. Evidence of serum and ionized magnesium metabolism disturbances have been observed in women with preeclampsia. This and the therapeutic utility of magnesium in preeclampsia led us to investigate the extent to which an endogenous tissue magnesium deficiency might be present in and contribute to its pathophysiology. We used 31 P nuclear magnetic resonance spectroscopy to noninvasively measure in situ intracellular-free magnesium levels in brain and skeletal muscle of fasting nonpregnant women (nϭ12), and of third trimester women with uncomplicated pregnancies (nϭ11) and preeclampsia (nϭ7). Compared with nonpregnant controls (brain 519Ϯ59 mol/L; muscle 604Ϯ34 mol/L), brain and skeletal muscle intracellular magnesium levels were significantly lower in both normal pregnant (brain 342Ϯ23 mol/L; muscle 482Ϯ40 mol/L; Pϭ0.05 for both tissues) and preeclamptic women (brain 229Ϯ17 mol/L; muscle 433Ϯ46 mol/L; Pϭ0.05 for both tissues). Brain intracellular magnesium was further reduced in preeclamptics compared with normal pregnant subjects (Pϭ0.05). For all pregnant subjects, blood pressure was significantly and inversely related to the concomitantly measured intracellular magnesium level in brain (systolic, rϭϪ0.59, Pϭ0.01; diastolic, rϭϪ0.52, Pϭ0.02) but not in muscle. Cellular magnesium depletion is characteristic of normal pregnancy and may be one factor contributing to the pathophysiology of preeclampsia. Furthermore, the influence of central nervous system factors on blood pressure may be mediated, at least in part, by ambient intracellular magnesium levels. Key Words: preeclampsia Ⅲ magnesium Ⅲ metabolism Ⅲ ions Ⅲ pregnancy H ypertension is the most common medical disorder during pregnancy. 1 The exact incidence of gestational hypertension-preeclampsia in the United States is unknown. Estimates indicates that 5% to 8% of all pregnant women will have preeclampsia, defined as hypertension and proteinuria beginning during the second half of gestation. 1 Preeclampsia may also be associated with increased neuromuscular irritability and seizures. 2 Interestingly neuromuscular excitability, vasoconstriction, elevated blood pressure (BP), and increased vascular sensitivity to pressor agents are also characteristic of magnesium (Mg) depletion. 3,4 The therapeutic use of intravenous Mg sulfate is universal, at least in the United States, for women with mild preeclampsia to prevent eclampsia seizures, 5,6 and its effectiveness has been confirmed in a recent metaanalysis showing that parental Mg more than halves the risk of eclampsia. 7 However, a clear role of Mg deficiency in the pathophysiology of preeclampsia has not been clearly established, 1,8,9 and dietary Mg supplementation does not seem to prevent the subsequent incidence of preeclampsia. 10 Our group has developed the use of 31 P nuclear magnetic resonance (...
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