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Biomedical subjects

L M Resnick

Publications and source records attributed to L M Resnick.

At least 55 records · Page 3Linked to original sources
PubMed1994

Vascular effects of 17 beta-estradiol in male Sprague-Dawley rats.

Bolus intravenous injections of 100 micrograms/kg 17 beta-estradiol significantly decreased the pressor responses to norepinephrine (NE; 0.3 microgram/kg) at the fourth, fifth, and sixth hour in anesthetized male Sprague-Dawley rats. At doses of 10(-6) to 3 x 10(-5) M, 17 beta-estradiol relaxed the sustained phase of contraction in male Sprague-Dawley rat tail artery helical strips precontracted in vitro by [Arg8]vasopressin (AVP), KCl, or NE. The effect was dose dependent. At doses of 3 x 10(-6) to 3 x 10(-5) M, it also decreased the initial phase of tension generation and extracellular Ca(2+)-dependent vasoconstriction induced by NE, AVP, or KCl in a dose-dependent manner in male Sprague-Dawley rat tail artery helical strips. 17 beta-Estradiol (2 x 10(-8) to 2 x 10(-6) M) decreased the voltage-dependent inward Ca2+ current and the intracellular free Ca2+ concentration ([Ca2+]i) increment induced by 15 mM KCl in a dose-dependent manner (3.6 x 10(-8) to 3.6 x 10(-6) M) in vascular smooth muscle cells (VSMC) isolated from male Sprague-Dawley rat tail arteries. We suggest that, at pharmacological doses, estrogen has a direct vasodilating effect on the rat tail artery that is mediated by its inhibitory effect on Ca2+ influx through voltage-dependent Ca2+ channels. The inhibitory effect of estrogen on the pressor responses to NE or AVP may be correlated with its modulation of VSMC [Ca2+]i through its actions on membrane Ca2+ channels.

Animals↗
PubMed1994

Intracellular ionic consequences of dietary salt loading in essential hypertension. Relation to blood pressure and effects of calcium channel blockade.

To study the ionic basis of salt sensitivity in hypertension, 19F-, 13P-, and 23Na-nuclear magnetic resonance techniques were used to measure cytosolic free calcium (Cai), pH (pHi), free magnesium (Mgi), and sodium (Nai) in erythrocytes of essential hypertensive subjects (n = 19). Individuals were studied for 2 mo each on low- (UNaV < 50 meq/d) and high- (UNaV > 200 meq/d) salt diets, with the concomitant administration of nifedipine (10 mg t.i.d.) or placebo tablets for 1 mo of each diet. Salt loading elevated Cai and Nai while suppressing Mgi and pHi; these changes occurred predominantly in salt-sensitive subjects (n = 9). Nifedipine blunted the pressor response to salt loading > 50% (delta diastolic BP [high-low salt vs placebo] = 5 +/- 2 vs 14 +/- 2 mmHg, P < 0.05) and reversed salt-induced ionic changes, lowering Cai and elevating Mgi and pHi. Regardless of the definition of salt sensitivity, continuous relationships were observed between the pressure response to salt loading, the levels of Cai (r = 0.726, P < 0.001), Nai (r = 0.747, P < 0.001), and pHi (r = -0.754, P < 0.001), and the salt-induced change in Mgi (r = -0.757, P < 0.001). Altogether, these results emphasize the reciprocal and coordinate nature of intracellular ionic changes in response to dietary salt loading and calcium channel blockade in essential hypertension. They suggest that salt sensitivity is mediated by cellular calcium accumulation from the extracellular space, in association with magnesium depletion and acidification. Lastly, interpretation of intracellular ion measurements in the future will require concurrent assessment of dietary salt intake.

Analysis of Variance↗
PubMed1994

Clinical studies with the NOVA ISE for IMg2+.

The Nova ISE for IMg2+ was utilized to examine IMg2+ in plasma and serum of patients with a variety of pathophysiologic and disease syndromes (e.g., long-term renal transplants [LTRT], during and before cardiac surgery, migraine headaches, head trauma, pregnancy, chronic fatigue syndrome [CFS], non-insulin dependent diabetes mellitus [NIDDM], asthma and after excessive dietary intake of Mg). The results indicate that LTRT treated with cyclosporin A, migraine, head trauma, pregnancy, NIDDM, diseased pregnant, and asthmatic patients all on the average, exhibit significant depression in IMg2+ but not total Mg (TMg). Patients with CFS failed to exhibit changes in serum IMg2+ or TMg levels. Increased dietary load of Mg, for only 6 days, resulted in significant elevations of serum IMg2+ but not TMg. Correlations between the clinical course of several of these syndromes and the fall in IMg2+ were found. The Ca2+/Mg2+ ratio appears to be an important guide for signs of peripheral vasoconstriction and or spasm and possibly enhanced atherogenesis. Overall, the data point to important uses for ISE's for IMg2+ in the diagnosis and treatment of disease states.

Calcium↗
PubMed1994

Serum-mediated intracellular calcium changes in normotensive and hypertensive red blood cells: role of parathyroid hypertensive factor.

To study cellular calcium metabolism in hypertension, we investigated the effects of human serum, and of the circulating pressor substance, parathyroid hypertensive factor (PHF), on the cytosolic free calcium (Cai-f) content of erythrocytes from normotensive and essential hypertensive subjects. In their own serum, basal Cai-f was higher in hypertensive than in normotensive and essential hypertensive subjects. In their own serum, basal Cai-f was higher in hypertensive than in normotensive subjects (mean +/- SEM; 39.4 +/- 4.0 vs. 23.4 +/- 2.7 nM; p < 0.05). Without serum, Cai-f was lower and not significantly different (23.0 +/- 3.1 vs. 18.2 +/- 2.7 nM; p = not significant). Addition of serum to serum-free erythrocytes increased Cai-f, and reestablished the Cai-f gradient in hypertensive cells (31.4 +/- 0.8 vs 23.0 +/- 2.3 nM; p < 0.05). PHF levels were directly related to basal Cai-f (r = -0.648; p < 0.05) and to the serum-induced rise in Cai-f (r = 0.600; p < 0.05). Furthermore, semipurified PHF, but not similarly prepared normotensive serum, increased Cai-f in normal human erythrocytes (PHF: +83.9 +/- 37.3% vs. +14.5 +/- 27.5%; p < 0.05). We conclude that circulating factors in general, and PHF in particular, may account for the increased basal Cai-f of hypertension, and thus at least partially contribute to te pathophysiology of the hypertensive process.

Aged↗
PubMed1994

The role of glucose in diabetic hypertension: effects on intracellular cation metabolism.

The clinical association of hypertension, obesity, noninsulin-dependent diabetes mellitus (NIDDM), and other cardiovascular risk factors has long been recognized. The recent finding that essential hypertension is also an insulin-resistant state associated with hyperinsulinemia led some authors to attribute a role in mediating this association and in the pathogenesis of hypertension itself to insulin. However, evidence also exists independently of insulin per se that alterations in glucose metabolism in general, and of hyperglycemia in particular, may also contribute to the hypertensive process, especially in the hypertension of diabetes. The authors attempted to understand the relationship between glucose and insulin metabolism, diabetes, and hypertension from a cellular ionic point of view. In vitro it was shown that glucose, in a specific, dose- and time-dependent manner, can directly and coordinately alter intracellular ions, increasing cytosolic free calcium, while suppressing intracellular free magnesium and pH levels. These glucose-induced changes exactly parallel those ionic lesions previously observed in vivo in the fasting hyperglycemia of hypertension associated with NIDDM. These and other data led to the hypothesis that circulating blood glucose, independently of insulin and even at normal levels, is a physiologic determinant of cellular ion homeostasis. Furthermore, the cellular ionic consequences of hyperglycemia may contribute to the increased risk of hypertension and vascular diseases present among subjects with NIDDM, impaired glucose tolerance, or both.

Animals↗
PubMed1994

Is the higher incidence of ischemic disease in patients with hypertension and diabetes related to intracellular depletion of high energy metabolites?

To study mechanisms underlying ischemia in hypertension and non-insulin dependent diabetes mellitus (NIDDM), 31P-magnetic resonance spectroscopy was used to evaluate adenosine triphosphate and 2,3 diphosphoglycerate (2,3 DPG) levels in erythrocytes of control (n = 21), hypertensive (n = 22), and NIDDM (n = 10) subjects. Compared to adenosine triphosphate levels in controls (2.22 +/- 0.10 mM), both hypertensive (1.89 +/- 0.10 mM, sig = 0.05 versus normal) and NIDDM subjects (1.57 +/- 0.13 mM, sig = 0.05 versus normal) exhibited lower values. NIDDM subjects also displayed suppressed levels of 2,3 DPG (6.84 +/- 0.48 mM, sig = 0.05 versus normal and EH), compared to hypertensives (8.34 +/- 0.27 mM). These data suggest cellular energy metabolism is disrupted in hypertension and NIDDM. Both conditions may thereby sensitize tissues to ischemic damage, lower adenosine triphosphate levels by decreasing energy reserves, and lower 2,3 DPG levels by inhibiting hemoglobin-oxygen dissociation.

2,3-Diphosphoglycerate↗
PubMed1994

Clinical aspects of parathyroid hypertensive factor.

Parathyroid hypertensive factor (PHF) in rats: PHF is an endogenous hypertensive substance which was originally associated with hypertension in spontaneously hypertensive rats (SHR). In this model, PHF was shown to act by increasing intracellular calcium levels in vascular smooth muscle and was linked with a characteristic pattern of abnormalities in overall calcium regulation. The action of PHF was blocked by calcium antagonists, suggesting that the effect of PHF was to increase extracellular calcium uptake. In SHR the parathyroid glands were shown to be the site of PHF secretion. This secretion was inhibited by an increase in dietary calcium. PHF was further shown to be unique to low-renin forms of hypertension, that is, those forms of hypertension characterized by abnormalities in calcium metabolism. PHF in humans: PHF was subsequently found in human low-renin salt-sensitive hypertension. As in SHR, calcium supplementation can lower PHF levels in humans. Similarly, there is circumstantial evidence for the parathyroid origin of PHF in humans. In human hypertensive patients, the presence of PHF has been shown to predict a favorable therapeutic response to calcium channel blockade. Recently, many of the abnormalities in calcium metabolism present in low-renin hypertension have also been described in other disease states. Notable among these diseases is non-insulin dependent diabetes mellitus. A survey of human non-insulin dependent diabetes mellitus has revealed that PHF was present in a disproportionate number of these patients independently of the blood pressure level. The significance of this latter finding needs to be explored, but PHF may prove to have relevance in diseases other than hypertension.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Calciotropic hormones in salt-sensitive essential hypertension: 1,25-dihydroxyvitamin D and parathyroid hypertensive factor.

HYPOTHESIS: Some, but not all, men and women display a pressor response to increases in dietary salt intake. The mechanism(s) underlying this salt-sensitive hypertension remains poorly defined. We have developed a hypothesis that all hypertension arises from an imbalance between mechanisms of cytosolic calcium accumulation from the extracellular space versus calcium release into the cytoplasm from intracellular storage sites. Extracellular calcium-dependent hypertension predominates in salt-sensitive subjects, while excess angiotensin II mediates the excess intracellular calcium release that is characteristic of renin-dependent salt-insensitive forms of hypertension. Studies on pressor hormones: We investigated potential etiologic factors mediating the cellular calcium accumulation in salt-sensitive hypertensive human subjects, and focused on two calcium-related circulating hormonal substances, 1,25-dihydroxyvitamin D and the recently described parathyroid hypertensive factor. Both of these substances directly facilitate calcium transport from the extracellular space in the cell. Furthermore, levels of these hormones are greatest in black normotensive and low-renin essential hypertensive subjects, both groups associated with salt-related hypertensive disease. Lastly, dietary salt loading elevates 1,25-dihydroxyvitamin D and parathyroid hypertensive factor levels, and the greater the level of either hormone, the greater the pressor response to salt. CONCLUSIONS: It is reasonable to consider that these salt-induced cellular ionophoric actions of 1,25-dihydroxyvitamin D and parathyroid hypertensive factor contribute, at least in part, to the mechanism of salt-sensitive hypertension in man.

Biological Factors↗
PubMed1993

Cellular ionic effects of insulin in normal human erythrocytes: a nuclear magnetic resonance study.

Elevated erythrocyte cytosolic free calcium, and suppressed free magnesium and pH values are associated with the hyperinsulinaemia and insulin resistance of hypertension, obesity, and Type 2 (non-insulin-dependent) diabetes mellitus. To determine the role of insulin in this process, we utilized 19F- and 31P-nuclear magnetic resonance spectroscopy to study the cellular ionic effects of insulin in vitro on normal human erythrocytes. Insulin elevated cytosolic free calcium levels in a dose- and time-dependent manner. The effect began at 10 microU/ml, peaked at 200 microU/ml, and continued at both the 500 microU/ml and 1000 microU/ml doses. At 200 microU/ml, free calcium levels rose from 24.6 +/- 2.5 nmol/l to a peak value at 120 min of 66.4 +/- 11 nmol/l (p < 0.05 vs basal), levels remaining elevated throughout the incubation (45.7 +/- 5.6 nmol/l at 60 min, and 47.9 +/- 9.1 nmol/l at 180 min, p < 0.05 vs basal, respectively). Similarly, insulin also increased intracellular free magnesium at all time points (basal: 177 +/- 11 mumol/l; 60 min: 209 +/- 19 mumol/l; 120 min: 206 +/- 22 mumol/l; and 180 min: 202 +/- 12 mumol/l; p < 0.05 vs basal at all times). No insulin-induced changes in pH were observed. We conclude: (i) that insulin in physiological concentrations may participate in regulating divalent cations in the mature human erythrocyte, (ii) that insulin per se cannot account for the previously described cellular ionic lesions of hypertension and diabetes, and (iii) that future clinical studies of cell ion metabolism should be conducted in the fasting state, be controlled for ambient circulating insulin levels, or both.

Calcium↗
PubMed1993

Intracellular and extracellular magnesium depletion in type 2 (non-insulin-dependent) diabetes mellitus.

To investigate alterations of magnesium metabolism in Type 2 (non-insulin-dependent) diabetes mellitus, we utilized a new magnesium-specific selective ion electrode apparatus to measure serum ionized magnesium (Mg-io) in fasting subjects with and without Type 2 diabetes, and compared these values to levels of serum total magnesium, and of intracellular free magnesium (Mgi) analysed by 31P-NMR spectroscopy. Both Mg-io (0.630 +/- 0.008 vs 0.552 +/- 0.008 mmol/l, p < 0.001) and Mgi (223.3 +/- 8.3 vs 184 +/- 13.7 mmol/l, p < 0.001), but not serum total magnesium, were significantly reduced in Type 2 diabetes compared with non-diabetic control subjects. Furthermore, a close relationship was observed between serum Mg-io and Mgi (r = 0.728, p < 0.001). We suggest that magnesium deficiency, both extracellular and intracellular, is a characteristic of chronic stable mild Type 2 diabetes, and as such, may predispose to the excess cardiovascular morbidity of the diabetic state. Furthermore, by more adequately reflecting cellular magnesium metabolism than total serum magnesium levels, Mg-io measurements may provide a more readily available tool than has heretofore been available to analyse magnesium metabolism in a variety of diseases.

Blood Glucose↗
PubMed1993

1,25-dihydroxyvitamin D as a cardiovascular hormone. Effects on calcium current and cytosolic free calcium in vascular smooth muscle cells.

Clinical and in vitro evidence suggests a role for the calcium regulating hormone, 1,25-dihydroxyvitamin D (1,25D) in human and experimental hypertension. To establish the cellular basis for this association, we utilized the whole-cell version of the patch clamp method and fluorescence spectroscopic techniques to measure voltage-dependent calcium channel activity and cytosolic free calcium concentrations ([Ca2+]i) in rat tail artery-derived smooth muscle cells, before and after the addition of 1,25D. 1,25D significantly increased the calcium channel current over the range of test pulses, from -40 to +60 mV, in a dose- and time-dependent manner, appearing by 5 to 10 min of exposure, with maximum effects by 15 min. At 10 and 30 nmol/L, the current increased to 149 +/- 10% and 221 +/- 13% of basal activity of 37.75 +/- 7.7 pA and 37.7 +/- 4.5 pA, respectively. Similarly, at 10 and 100 nmol/L, 1,25D increased cytosolic free calcium levels 115 +/- 2% and 171 +/- 11%, from basal values of 99 +/- 32 nmol/L and 116 +/- 10 nmol/L, respectively. These effects of [Ca2+]i developed slowly over 3 to 4 min. Peak values were achieved by 30 min of incubation and were reversible with removal of 1,25D from the medium. Altogether, these direct effects of 1,25D on calcium current and [Ca2+]i in vascular smooth muscle cells support a role for 1,25D in vascular physiology, and provide a cellular basis for better understanding the involvement of 1,25D in hypertensive vascular disease.

Animals↗
PubMed1993

Independent effects of hyperinsulinemia and hyperglycemia on intracellular sodium in normal human red cells.

To study the contribution of glucose vis-à-vis insulin in the altered sodium homeostasis of diabetes mellitus, we utilized 23Na-NMR spectroscopy to noninvasively measure intracellular sodium (Nai) in red blood cells of non-diabetic, thin, normotensive subjects (n = 9), before and 60, 120, and 180 min after in vitro incubation with elevated glucose (15 mmol/L) and insulin (200 mumol/L) concentrations. Hyperglycemia caused a significant rise in Nai compared to basal values at 60 (9.1 +/- 0.8 to 9.7 +/- 0.8 mEq/L, P < .05), and 120 min (10.0 +/- 0.7 mEq/L, P < .05 v basal). Hyperinsulinemia induced a more pronounced and prolonged elevation of Nai. Significant elevations occurred at 60 (8.0 +/- 0.5 to 10.2 +/- 0.7 mEq/L, P < .05), 120 (10.5 +/- 1.1) mEq/L, P < .05 v basal), and 180 (9.1 +/- 0.5 mEq/L, P < .05 v basal) minutes. Thus, both hyperinsulinemia, and to a lesser extent, hyperglycemia cause intracellular sodium accumulation in normal human red cells. Since glucose transport in red cells is not insulin-dependent, insulin and glucose presumably exert their effects independently. Altogether, we suggest that these insulin- and glucose-mediated effects on cellular sodium, if present in other tissues as well, may underlie the increased total body sodium and the salt-dependent hypertension characteristic of chronic diabetic or hyperinsulinemic syndromes.

Erythrocytes↗
PubMed1993

Ionic basis of hypertension, insulin resistance, vascular disease, and related disorders. The mechanism of "syndrome X".

Great pathophysiological significance has recently been placed on the association of metabolic abnormalities, such as hyperinsulinemia, insulin resistance, obesity, and frank diabetes mellitus, with essential hypertension and coronary artery disease, and the clinical coincidence of these features has been termed "syndrome X." Despite the suggestion that insulin itself mediates this clinical linkage, the specific mechanisms underlying this syndrome remain poorly understood. We have attempted to understand these phenomena at the cellular level, and have investigated the role of cellular mineral ion species such as cytosolic free calcium (Cai), free magnesium (Mgi), and intracellular pH (pHi) in various insulin resistant states, including essential hypertension, obesity, and type II (non-insulin-dependent) diabetes mellitus (NIDDM). Utilizing nuclear magnetic resonance spectroscopic techniques to noninvasively assess intracellular concentrations of these ions, we observed that each of these disease states is characterized, in whole or in part, by common abnormalities of cellular ion metabolism, including elevated Cai levels and suppressed levels of Mgi and pHi. Furthermore, despite the predominant use of red cells as a tissue source, the measured levels of Cai, Mgi, and pHi were closely related to the ambient blood pressure, the degree of cardiac hypertrophy, and to the hyperinsulinemic response to oral glucose challenge. Altogether, these data suggest an integrated "ionic hypothesis" in which the frequent clinical coexistence of hypertension and altered insulin metabolism derives from common abnormalities of cellular ion handling, resulting in excess steady-state levels of Cai, reciprocal depletion of Mgi, and lowered pHi. These cellular ion alterations would be expected to have tissue-specific consequences, appearing in vascular tissue as vasoconstriction and elevated blood pressure, in skeletal muscle and fat as insulin resistance, in pancreatic beta-cells as hyperinsulinemia, and in neural tissue as potentiated neurotransmitter release and increased sympathetic nerve activity. Thus, according to this hypothesis, essential hypertension, insulin resistance, hyperinsulinemia, and NIDDM are in reality different clinical components of what should be better designated as "generalized cardiovascular-metabolic disease" (GCMD).

Animals↗
PubMed1993

Ionic basis of hypertension in diabetes mellitus. Role of hyperglycemia.

Alterations of cell ion content have been reported acutely after oral glucose ingestion, and chronically in subjects with hypertension and noninsulin dependent diabetes mellitus (NIDDM). We have hypothesized that these ionic abnormalities, elevated cytosolic free calcium (Cai), and suppressed intracellular pH (pHi) and free magnesium (Mgi), common to both of these syndromes, may explain their frequent clinical coincidence. To investigate the potential role of glucose in this process, we utilized 19F- and 31P-NMR spectroscopy to measure Cai, Mgi, and pHi in normal human red blood cells before and 60, 120, and 180 min after in vitro incubation with glucose (15 mmol/L) and equimolar concentrations of the glucose analogs, L-glucose, 2-deoxyglucose, and 3-O-methylglucose. At each point in time (from t = 0 to t = 60, 120, 180 min), glucose induced significant (P < .05) elevations in Cai (27.2 +/- 2.2 to 68.3 +/- 7.2, 70.7 +/- 10.5, 59.8 +/- 10.1 nmol/L), while suppressing pHi (7.28 +/- 0.02 to 7.22 +/- 0.03, 7.23 +/- 0.03, 7.22 +/- 0.03), and Mgi (206 +/- 10 to 151 +/- 7, 131 +/- 7, 143 +/- 5 mumol/L). This glucose induced ionic effect was dose dependent, significant elevations in Cai being observed at 10 and 15 mmol/L, but not at the other concentrations tested. It was also specific, no changes in Cai being observed with any of the glucose analogs tested. Thus, hyperglycemia per se elevates Cai and suppresses Mgi and pHi in normal human red cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Blood Glucose↗
PubMed1993

Sex hormones and hemostatic risk factors for coronary heart disease in men with hypertension.

OBJECTIVE AND DESIGN: It has been hypothesized that risk factors for coronary heart disease in men are linked and that the underlying factor linking them may be an alteration in the sex hormone milieu. As a test of this hypothesis, sex hormones and fibrinogen, factor VII and plasminogen activator inhibitor (PAI-1), hemostatic factors recently shown to be risk factors for myocardial infarction, were measured in men with hypertension and in healthy control subjects. RESULTS: The fasting serum testosterone and free testosterone levels were decreased and the plasma factor VII and PAI-1 levels increased in the men with hypertension. CONCLUSION: These findings are consistent with the stated hypothesis.

Blood Coagulation Factors↗
PubMed1993

Relation of hemostatic risk factors to other risk factors for coronary heart disease and to sex hormones in men.

The present study was carried out to explore the possible relation of plasma plasminogen activator inhibitor-1 (PAI-1), fibrinogen, and factor VII levels to other risk factors for coronary heart disease (CHD) and to serum sex hormone levels. The study group comprised 48 apparently healthy men. To avoid the confounding factor of obesity, correlations were determined in the 30 men in this group with a body mass index (BMI) < 26.4, after controlling for age. PAI-1 correlated with testosterone, estradiol/testosterone, and free testosterone/testosterone (FT/T), and fibrinogen correlated with FT/T. All three hemostatic factors correlated with glucose and with the ratio of cholesterol/high density lipoprotein cholesterol, while PAI-1 correlated with diastolic blood pressure. To test the effect of obesity, correlations were determined in the entire group of 48 men, which included 18 subjects with a BMI > 26.4. All three hemostatic factors correlated with BMI in this group after controlling for age; however, on controlling for testosterone, only PAI-1 correlated with BMI. Fibrinogen correlated with age in both groups after controlling for testosterone or BMI. These correlations support the hypothesis that PAI-1, fibrinogen, and factor VII are related to other risk factors for CHD and that an alteration in the sex hormone milieu may be the underlying factor linking them.

Adult↗
PubMed1993

Diabetes, hypertension and atherosclerosis: pathophysiological role of intracellular ions.

The clinical coincidence of hypertension, obesity and non insulin diabetes mellitus (NIDDM) has long been recognized. Increasing interest has also been recently focused on the possible role of insulin and insulin resistance in mediating this association. There is also evidence that hyperglycemia per se may have a role in the pathogenesis of hypertension and atherosclerosis in NIDDM patients. Glucose is a determinant to cellular ion homeostasis, promoting an increase of intracellular calcium and suppressing intracellular free magnesium and pH. Moreover, hyperglycemia promotes glycosilation of proteins and the consequent accumulation of advanced glycosilation end products in tissues. It has recently been suggested that iter is a cellular ionic basis for the clinical and epidemiological linkage of hypertension, left ventricular hypertrophy (LVH), obesity and non insulin dependent diabetes mellitus (NIDDM). These clinical conditions may be different expressions of a common underlying defect in ion handling, displayed by elevated cytosolic free calcium and suppressed free magnesium levels. Therapeutically, reversal of this excess free calcium accumulation and/or free magnesium deficit with ion specific agents, such as calcium channel blocker drugs, may thus ameliorate not only the elevated blood pressure of hypertension but also the concurrent cardiac, vascular and metabolic aspects of the hypertensive states.

Arteriosclerosis↗