Therapeutic implications of calcium intake in hypertension: more analyses, a little progress, and a different approach.
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Aged↗
Biomedical subjects
L M Resnick
Publications and source records attributed to L M Resnick.
Comprehensive nutrition plan improves cardiovascular risk factors in essential hypertension.
Increased arterial pressure is known to be influenced by a variety of nutrients. Compliance with dietary recommendations for risk reduction is often limited by the complexity of their implementation. In addition, how improvements in total diet, rather than single nutrients, influence concomitant cardiovascular risk factors has not been thoroughly explored. We assessed the effects of a nutritionally complete prepared meal program, the Campbell's Center for Nutrition and Wellness plan (CCNW), compared with dietary therapy in which participants received a structured nutritional assessment and prescription and selected their own foods, in 101 women and men with mild-to-moderate hypertension. Outcome measures included blood pressure (BP), lipids and lipoproteins, glucose, glycosylated hemoglobin (HbA1c), insulin, homocysteine, nutrient intake, compliance, and quality of life. Both dietary interventions significantly lowered BP (P < .0001), while simultaneously improving the overall cardiovascular risk profile. Significantly greater benefits were observed with the CCNW plan as compared with the participant selected diet in cholesterol and LDL levels (both P < .0001), LDL:HDL (P < .001), HbA1c (P < .05), homocysteine (P < .001), total nutrient intake (P < .0001), compliance (P < .0001), and quality of life (P < .001). This study demonstrates that improving the total diet to include the full array of recommended dietary guidelines, rather than focusing on single nutrients, has significant benefits for the cardiovascular risk profile of hypertensive persons beyond BP control. Compared with typical dietary therapy, the comprehensive CCNW meal plan has significantly greater effects on multiple cardiovascular risk factors while yielding greater compliance and improved quality of life.
Adult↗
Magnesium responsiveness to insulin and insulin-like growth factor I in erythrocytes from normotensive and hypertensive subjects.
Depletion of intracellular free magnesium (Mg(i)) is a characteristic feature of insulin resistance in essential hypertension, but it is not clear to what extent low Mg(i) levels contribute to insulin resistance, result from it, or both. As insulin-like growth factor I (IGF-I) may improve insulin resistance, we investigated whether this peptide could similarly improve Mg(i) responsiveness to insulin in hypertension, and whether this effect was related to any direct IGF-I effect on Mg(i). 31P-Nuclear magnetic resonance spectroscopy was used to measure Mg(i) in erythrocytes from 13 fasting normotensive and 10 essential hypertensive subjects before and 30, 60, and 120 min after incubation with a physiologically maximal dose of insulin (200 microU/mL) and with different doses of recombinant human IGF-I (0.1-100 nmol/L). In normotensive subjects, IGF-I elevated Mg(i) (P < 0.05) in a dose- and time-dependent fashion, as did insulin (P < 0.05). However, in hypertensive subjects, maximal Mg(i) responses to insulin, but not to IGF-I, were blunted [insulin, 163+/-11 to 177+/-10 micromol/L (P=NS); IGF-I, 164+/-6 to 190+/-11.7 micromol/L (P < 0.05)]. Furthermore, for insulin, but not for IGF-I, cellular Mg(i) responsiveness was closely and directly related to basal Mg(i) levels (insulin: r=0.72; P < 0.01; IGF-I: r=0.18; P=NS). Lastly, blunted Mg(i) responses to insulin could be reversed by preincubation of hypertensive cells with IGF-I. We conclude that 1) both IGF-I and insulin stimulate erythrocyte Mg(i) levels; 2) cellular Mg(i) responses to insulin, but not to IGF-I, depend on basal Mg(i) levels, i.e. the higher the Mg(i) the greater the sensitivity to insulin; and 3) IGF-I potentiates insulin-induced stimulation of Mg(i) at doses that themselves do not raise Mg(i). These effects of IGF-I may underlie at least in part its ability to improve insulin sensitivity clinically. Together, these data support a role for IGF-I in cellular magnesium metabolism and emphasize the importance of magnesium as a determinant of insulin action.
Adult↗
Physiologic rationale for calcium antagonist therapy in essential hypertension.
Two basic concepts that are relevant to hypertensive cardiovascular disease are often ignored despite being central to a proper understanding and clinical approach to our patients. First, high blood pressure is an abnormal physical sign; a 'vital' sign, as are temperature, pulse, and respiration. Although people often consider hypertension as a disease, it is itself not a disease, but rather one sign of a disease: a warning manifestation of a disease. Approximately 90% of the time, the underlying cause(s) of this sign are unknown and, thus, the condition itself is named according to its sign, as essential hypertension. Commonly, physicians are told that by eliminating the messenger bearing the bad news--i.e., by merely suppressing the blood pressure, the excess morbidity and mortality associated with the underlying disease process will be reversed. Unfortunately, the cumulative experience of over two decades of world-wide clinical trials indicates that getting rid of only one aspect of hypertensive disease, the elevated blood pressure, gets rid of only part of the excess cardiovascular risk associated with hypertension. By contrast, we now appreciate that what we call hypertension carries with it other peripheral manifestations present in other body systems, such as left ventricular hypertrophy, that may exist prior to and progress independently of the hypertension itself; and insulin resistance, reflecting the same underlying pathophysiology in skeletal muscle, fat, and other tissues. Thus, the disease we call hypertension is not just a 'numbers' game. As such, a reasonable goal not yet attained would be to identify common factors underlying not only the elevations of blood pressure, but the other multisystemic aspects of hypertensive cardiovascular disease as well. Focusing on such underlying factors would allow treatment of the disease process itself, rather than just the level of blood pressure. A second concept, also often overlooked but quite obvious, is the pathophysiologic and clinical heterogeneity of hypertension. People are different. By analogy with an elevated temperature, the same elevation of blood pressure that leads to the diagnosis of 'essential' hypertension may result from many different "primary" causes, which just happen to have hypertension as one shared clinical manifestation. This immediately implies that when we ask, "Is this drug good, or preferred for hypertension?" the answer should be, "It depends." As an obvious example, to be discussed in more detail below, the salt-sensitive hypertensive responds to dietary salt recommendations and to different drug classes differently from an individual who is not salt-sensitive.
Administration, Oral↗
Nutritional management of cardiovascular risk factors. A randomized clinical trial.
BACKGROUND: Adherence to dietary recommendations for disease management is often hindered by the complexity of incorporating them into the daily diet. Nutrition and cardiovascular scientists and food technologists collaborated to develop a prepared meal plan that meets national dietary guidelines for cardiovascular risk reduction. OBJECTIVE: To assess the clinical effects of this plan, which incorporates all National Academy of Sciences National Research Council recommended dietary allowances for vitamins, minerals, and macronutrients, compared with a patient-selected American Heart Association Step I and Step II diet plan. METHODS: This multicenter, randomized, parallel-intervention trial was conducted at 10 medical centers in the United States and Canada and involved 560 men and women with hypertension, dyslipidemia, or diabetes. Following calculation of prescriptions to meet individual nutritional requirements based on the Harris-Benedict equation, participants were randomized to the Campbell's Center for Nutrition and Wellness (CCNW) plan, which is composed of prepackaged breakfast, lunch, and dinner meals provided to participants, or a nutritionist-guided American Heart Association Step I and Step II diet, in which participants self-selected foods to meet their nutrition prescription for 10 weeks. MAIN OUTCOME MEASURES: Blood pressure (BP); lipid, glucose, glycosylated hemoglobin (HbA1c), and insulin levels; body weight; dietary intake; and quality of life. RESULTS: Patients' BP, lipid levels, carbohydrate metabolism, weight, and quality of life (P < or = .001 for all findings except low-density lipoprotein-high-density lipoprotein ratio, P = .25) all improved on both nutrition plans. Mean differences (+/-SD) between baseline and treatment clinical values for the CCNW and the self-selected diet groups (between-group P values), respectively, were as follows: systolic BP, -6.4 +/- 9.2 mm Hg and -4.6 +/- 9.0 mm Hg (P = .02); diastolic BP, -4.2 +/- 5.7 mm Hg and -3.0 +/- 5.1 mm Hg (P = .006); cholesterol, -0.32 +/- 0.58 mmol/L and -0.27 +/- 0.56 mmol/L (-12.4 +/- 22.5 mg/dL and -10.4 +/- 21.9 mg/dL) (P = .30); glucose, -0.65 +/- 1.88 mmol/L and -0.75 +/- 2.03 mmol/L (-11.7 +/- 34.0 mg/dL and -13.5 +/- 36.6 mg/dL) (P = .10); and HbA1c, -0.4% +/- 0.8% and -0.3% +/- 0.7% (P = .66). Weight loss with the CCNW and self-selected plans, respectively, was as follows: men, -4.5 +/- 3.6 kg and -3.5 +/- 3.3 kg; and women, -4.8 +/- 3.0 kg and -2.8 +/- 2.8 kg. Quality of life was significantly improved for daily and work activities (P < .05) and nutritional health perceptions (P < .05) with the CCNW plan relative to the self-selected group. Overall nutrient intake and compliance were both significantly (P < .001) better with the CCNW plan. CONCLUSIONS: Nutritionally balanced meals that meet the recommendations of national health organizations improved multiple risk factors for patients with cardiovascular disease. The CCNW plan resulted in greater clinical benefits, nutritional completeness, and compliance than the self-selected diet. The CCNW is a comprehensive nutrition plan, convenient for both prescription and practice, and appears viable for effecting favorable dietary changes in patients at high risk for cardiovascular disease.
Adult↗
Magnesium in the pathophysiology and treatment of hypertension and diabetes mellitus: where are we in 1997?
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Animals↗
Serum ionized magnesium: relation to blood pressure and racial factors.
To study potential ionic factors predisposing to vascular disease in hypertension, particularly among black subjects, we used a recently developed combined magnesium and calcium specific, ion selective electrode apparatus to measure extracellular ionized calcium (Ca-ion), ionized magnesium (Mg-ion), and Ca-ion/Mg-ion ratios in the serum of fasting, nonmedicated white and black normotensive (n = 61) and hypertensive (n = 23) subjects, studied consecutively in a tertiary referral center. Both race and blood pressure status had independent effects on the distribution of Mg-ion values. Although Mg-ion levels for the group as a whole were lower in hypertensive versus in normotensive subjects (0.571+/-0.012 v 0.601+/-0.005 mmol/L; P < .01), this was only true of white subjects (0.579+/-0.021 v 0.620+/-0.006 mmol/L; P = .0095). The lack of a significant difference in Mg-ion levels between black hypertensive versus normotensive subjects (0.553+/-0.012 v 0.577+/-0.007 mmol/L, P = NS) was attributable to the significantly lower Mg-ion levels present in normotensive blacks compared to those in normotensive white subjects (0.577+/-0.007 v 0.620+/-0.006 mmol/L, P = .0001). Resultant Ca-ion/Mg-ion ratios were elevated in all black subjects and in white hypertensive subjects. These data support the presence among hypertensives and among black subjects (independently of blood pressure) of a consistent depletion of circulating magnesium and of an imbalance of calcium and magnesium that may potentiate vascular disease among these subjects.
Black People↗
Dietary compliance and cardiovascular risk reduction with a prepared meal plan compared with a self-selected diet.
Noncompliance with therapeutic diets remains a major obstacle to achieving improvements in cardiovascular disease (CVD) morbidity and mortality. This study compared dietary compliance and CVD risk factor response to two dietary interventions designed to treat hypertension, dyslipidemia, and diabetes mellitus. In a multicenter trial, 560 adults were randomly assigned to either a self-selected, mixed-food plan (n = 277), or a nutrient-fortified prepared meal plan (n = 283); each was designed to provide 15-20% of energy from fat, 55-60% from carbohydrate, and 15-20% from protein. Nutrient intake was estimated from 3-d food records collected biweekly throughout the 10-wk intervention. Compliance was determined by evaluating the participants' ability to meet specific criteria for energy intake [+/-420 kJ (100 kcal) from the midpoint of the prescribed energy range], fat intake (< 20%, < 25%, or < 30% of energy from total fat), and the National Cholesterol Education Program/American Heart Association Step 1 and 2 diet recommendations. Compliance with energy, fat, and Step 1 and 2 criteria was better in participants who followed the prepared meal plan than in those who followed the self-selected diet (P < 0.0001). Compliant participants in both groups achieved greater reductions in body weight, systolic and diastolic blood pressure, and total and low-density-lipoprotein cholesterol than noncompliant participants (P < 0.05). In general, better endpoint responses were observed with lower fat intakes regardless of group assignment. The prepared meal plan is a simple and effective strategy for meeting the many nutrient recommendations for CVD risk reduction and improving dietary compliance and CVD endpoints.
Adult↗
Direct magnetic resonance determination of aortic distensibility in essential hypertension: relation to age, abdominal visceral fat, and in situ intracellular free magnesium.
To investigate the contribution of vascular compliance to essential hypertension (EH), we developed magnetic resonance imaging (MRI) techniques to directly measure aortic distensibility (AD) in the ascending and descending thoracic and abdominal aorta of fasting normal (n= 10) and EH (n=20) subjects. These results were compared with concurrent MR-based measurements of left ventricular mass index (LVMI) and abdominal subcutaneous and visceral fat and with 31P-MR spectroscopic measurement of in situ intracellular free magnesium levels (Mgi) in brain and skeletal muscle. Aortic distensibility in EH was consistently and significantly reduced at all measured sites (2.5+/-0.4, 2.2+/-0.4, 2.3+/-0.4 versus 7.0+/-1.6, 5.1+/-0.3, 7.3+/-0.8 mm Hg(-1) x 10(-3), P<.05), as was Mgi in the brain (284+/-22 versus 383+/-34 micromol/L, P<.05) and skeletal muscle (397+/-10 versus 527+/-36 micromol/L, P<.05). For all subjects, systolic blood pressure (r=-.662, P<.0001) and LVMI (r=-.484, P<.01) were inversely related to AD. AD and brain Mgi were inversely related to age (AD, r=-.792, P<.0001; brain Mgi: r=-.673, P<.05). AD was inversely related to fasting blood glucose (r=-.413, P<.05) and to abdominal visceral fat (r=-.416, P<.05) but not to body mass index (BMI: r=-.328, P=NS) or subcutaneous fat (r=-.157, P=NS). AD was also significantly and positively related to in situ Mgi, both in the brain and skeletal muscle (brain: r=.712, P<.01; skeletal muscle: r=.632, P<.01). We conclude that (1) MR techniques can be used to coordinately and noninvasively assess cardiac, vascular, metabolic, and ionic aspects of hypertensive disease in humans; (2) increased systolic blood pressure and LVMI in EH may at least in part result from decreased AD; (3) decreased Mgi contributes to arterial stiffness in hypertension and may help to explain the characteristic age-related decreases in AD; and (4) decreased AD may be one mechanism by which abdominal visceral fat contributes to cardiovascular risk.
Adult↗
Altered ionic effects of insulin in hypertension: role of basal ion levels in determining cellular responsiveness.
To investigate the ionic actions of insulin in hypertension, 19F- and 31P-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 = 9) and hypertensive (n = 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 +/- 2.2 vs. 19.8 +/- 2.5 nmol/L; P < 0.05), and basal Mg(i) levels were significantly lower (170 +/- 10.9 vs. 209 +/- 8 micromol/L; P < 0.05) than in normotensive subjects. In normal cells, insulin significantly elevated Ca(i) to 39.8 +/- 8.0, 50.1 +/- 8.2, 69.3 +/- 11.1, and 50.9 +/- 13.4 nmol/L at 30, 60, 120, and 180 min and Mg(i) to 238 +/- 10,264 +/- 14,226 +/- 11, and 216 +/- 10 micromol/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 = -0.574; P = 0.013), and the lower the Mg(i), the less Mg(i) rose (r = 0.524; P = 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 = 0.637; P < 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.
Adult↗
Diabetes mellitus, hypertension and ageing: the ionic hypothesis of ageing and cardiovascular-metabolic diseases.
Ageing in industrialised societies is associated with an increasing prevalence of hypertension, atherosclerotic vascular diseases, reduced insulin sensitivity and non-insulin-dependent diabetes mellitus (NIDDM). It has been suggested that hyperinsulinaemia/insulin resistance and/or hyperglycaemia could play a role in determining and/or exacerbating the hypertension and vascular disease associated with diabetes mellitus and ageing. Insulin-resistant states, such as essential hypertension and NIDDM, as well as "normal" ageing, are characterised by similar intracellular ionic defects, i.e. accumulation of cytosolic free calcium and depletion of free magnesium. The importance of calcium and magnesium ions in regulating cell functions is well-known. A rise in cellular free calcium and a depletion in cellular magnesium may induce cellular insulin resistance and vasoconstriction. Ionic levels quantitatively predict the extent of elevated blood pressure, fasting blood glucose, HBA1c and hyperinsulinaemic response to oral glucose challenge. We suggest that ionic disturbance might be the missing link responsible for the frequent clinical coexistence of hypertension, atherosclerosis and metabolic disorders. Ageing cells may become more vulnerable to ion disturbances, leading to possible elevation of intracellular free calcium and concurrent magnesium depletion. The "ionic hypothesis" of ageing supposes that an alteration in the cellular mechanisms which maintain the homeostasis of cytosolic calcium concentrations may play a key role in the ageing process, and that a sustained accumulation of cellular calcium and/or the depletion of cellular magnesium may also provide the final common pathway for many ageing-associated diseases, including hypertension and NIDDM.
Aging↗
Improved quality of life in patients with generalized cardiovascular metabolic disease on a prepared diet.
Current dietary recommendation for cardiovascular disease risk reduction and recommended dietary allowances (RDAs) were used to develop a nutritionally complete prepackaged prepared meal plan specifically designed to reduce the risk of cardiovascular disease. In the current study we tested patient acceptance of the diet as defined by measures of quality of life. In a randomized, parallel-design, multicenter clinical trial, 77 persons with hypertension, diabetes mellitus, dyslipidemia, or a combination of two or more of these conditions were recruited and randomly assigned to either a prepared meal plan (n = 39) or a comparable self-selected diet (n = 38) for 10 wk. The prepared meal plan met both the RDAs for all essential micronutrients and the dietary recommendations of national health organizations for macronutrients, cholesterol, sodium, and fiber. The prescribed self-selected diet was matched for macronutrients. Quality of life, as measured by a battery of instruments, was the major endpoint. Individuals consuming the prepared meal plan had significant improvements in mental health (P < 0.01), general perceived health (P < 0.005), daily activities (P < 0.05), work performance (P < 0.005), affect (P < 0.01), and nutritional health perceptions (P < 0.001), and reductions in nutrition hassles based on a standardized questionnaire (P < 0.001). The self-selected-diet group had significant improvements in nutritional health perceptions (P < 0.001) and affect (P < 0.001). There were significant improvements in weight (P < 0.001), blood pressure (P < 0.001), cholesterol (P < 0.002), low-density lipoproteins (P < 0.001), glucose (P < 0.014), and glycated hemoglobin (Hb A(1c) (P < 0.004) that were comparable in both groups. In summary, this study shows that a nutritionally complete diet, whether prepackaged or self-selected, improves multiple risk factors for cardiovascular disease. The prepackaged prepared meal plan had the added benefit of a greater improvement in quality of life.
Blood Glucose↗
Altered cellular calcium responsiveness to insulin in normal and hypertensive pregnancy.
OBJECTIVE: To investigate the glucose-independent calcium-related effects of insulin from subjects with normal and hypertensive pregnancies. METHOD: We used lndo-l fluorescence spectroscopy to measure cytosolic free calcium levels (Cai) in peripheral blood mononuclear cells (PBM) from 17 women (aged 20-40 years), six nonpregnant controls (NPC), five pregnant normotensive (PNT) women and six pregnant hypertensive (PHT) women, before and 5, 30, 60, 120 and 180 min after in vitro incubation with 200 microU/ml insulin. RESULTS: Basal Cai levels were significantly higher in PHT women (175.2 +/- 18.8 nmol/l) than they were in NPC women (122.8 +/- 2.8 nmol/l) and PNT women (123.9 +/- 3.5 nmol/l). The initial insulin-induced rise in Cai was similar in NPC (delta Cai 13.5 +/- 5.6 nmol/l) and PNT women (delta Cai 14.6 +/- 3.7 nmol/l), but appeared blunted in PHT women (delta Cai 8.2 +/- 3.5 nmol/l), and, for all pregnant subjects, was closely and inversely related to basal Cai. Over time, in PNT women, delta Cai did not increase from the initial response (maximal delta Cai 20.5 +/- 2.3 nmol/l) compared to NPC. The total cellular calcium response to insulin was also blunted in PNT women (the area under the calcium-responses curve was 86 +/- 3.4 versus 97.4 +/- 6.5 nmol/l), but was excessive in PHT women (115.5 +/- 6 nmol/l, P = 0.05). CONCLUSIONS: Hypertension in pregnancy is associated with excess Cai, insulin raises Cai in PBM, and different alterations of Cai responsiveness to insulin occur both in normal and in hypertensive pregnancy. These cellular calcium alterations may help to explain altered tissue responsiveness to insulin and other hormones in pregnancy.
Adult↗
Cellular ions in NIDDM: relation of calcium to hyperglycemia and cardiac mass.
OBJECTIVE: To investigate the role of hyperglycemia in mediating the clinical association of NIDDM with hypertension and left ventricular dysfunction and hypertrophy. RESEARCH DESIGN AND METHODS: Since hyperglycemia elevates cytosolic free calcium (Cai) both in myocardial and vascular smooth muscle cells, we utilized nuclear magnetic resonance (NMR) spectroscopy to measure erythrocyte Cai levels and compared them with serum ionized calcium (Caio), glucose, and insulin values before and following an oral glucose tolerance test (OGTT) and with previously obtained cardiac structural indexes in normotensive and hypertensive NIDDM (n = 32) and normal control subjects (n = 35). RESULTS: Compared with control subjects, normotensive NIDDM subjects had higher Cai (31.5 +/- 2.3 vs. 24.3 +/- 1.9 nmol/l, P = 0.05), lower intracellular free magnesium (Mgi) (200 +/- 10 vs. 225 +/- 7 mumol/l, P = 0.05), and greater posterior wall thickness (0.98 +/- 0.04 vs. 0.86 +/- 0.03 cm, P = 0.05). Hypertensive NIDDM subjects exhibited a further increase in Cai (43.1 +/- 4.4 nmol/l, P = 0.05 vs. control subjects) and left ventricular mass (LVM) (201.5 +/- 12.2 vs. 155.8 +/- 7.7 g, P = 0.05 vs. control subjects). For all subjects, significant relationships were observed between Cai and fasting blood glucose (r = 0.510, P < 0.01), HbAic (r = 0.389, P < 0.05), and the glycemic response to OGTT (the area under the curve [AUC] for glucose; r = 0.519, P < 0.01) and to systolic (r = 0.504, P < 0.01) and diastolic (r = 0.624, P < 0.01) blood pressure. Left ventricular mass index (LVMI) was related to fasting glucose levels (r = 0.406, P < 0.01) and the AUC for glucose (r = 0.380, P < 0.01), but not to fasting insulin or insulin responses to an OGTT. The LVMI was best related to Cai (r = 0.516, P < 0.01), while being inversely related to Caio (r = -0.486, P < 0.01). Multivariate regression indicated the contribution of glucose to LVMI was independent of age, BMI, insulin, and blood pressure but demonstrated a significant interaction with Cai. CONCLUSIONS: Altogether, these data suggest that glucose-related excess Cai is a fundamental lesion in diabetes that contributes to the elevated blood pressure and cardiac mass in this disease.
Blood Glucose↗
Extracellular and intracellular magnesium depletion in pregnancy and gestational diabetes.
OBJECTIVE: Our purpose was to investigate a possible ionic basis linking pregnancy and gestational diabetes with the vascular disorders associated with them. STUDY DESIGN: We used phosphorus 31 nuclear magnetic resonance spectroscopy and magnesium- and calcium-specific ion electrodes to measure erythrocyte intracellular free magnesium, plasma ionized magnesium, and ionized calcium in fasting nonpregnant (n = 26), normal pregnant (n = 20), and diet-controlled (class A1) gestational diabetic women (n = 13). RESULTS: Compared with nonpregnant controls (total magnesium 0.91 +/- 0.07 mmol/L, ionized magnesium 0.51 +/- 0.03 mmol/L), total and ionized magnesium were significantly lower in both normal pregnant (total magnesium 0.72 +/- 0.07 mmol/L, ionized magnesium 0.46 +/- 0.02 mmol/L, significance < 0.0001) and gestational diabetic (total magnesium 0.74 +/- 0.05 mmol/L, ionized magnesium 0.46 +/- 0.02 mmol/L, significance < 0.0001) subjects. Gestational diabetic women had significantly lower intracellular free magnesium values compared with nonpregnant and normal pregnant individuals (140 +/- 20 mumol/L vs 169 +/- 27 mumol/L, significance = 0.007). Ionized calcium values were similar in all groups, resulting in significant elevation (significance < 0.0001) of ionized calcium/ionized magnesium ratios in both pregnant groups. CONCLUSIONS: These results support the presence of magnesium depletion in pregnancy itself and to a greater extent in gestational diabetes. We suggest that magnesium depletion, or relative calcium excess, may predispose to vascular complications of pregnancy.
Adult↗
"Physiologic" intracellular acidosis in pregnancy.
To investigate acid-base homeostasis in pregnancy, we used phosphorus 31 nuclear magnetic resonance spectroscopy to measure intracellular pH in erythrocytes from nonpregnant (n = 33) and third-trimester pregnant women (n = 22). Intracellular pH was lower in pregnant compared with nonpregnant controls (7.23 +/- 0.015 vs 7.29 +/- 0.012, p = 0.003). We hypothesize that this "physiologic" intracellular acidosis of pregnancy potentiates oxygen-hemoglobin dissociation and oxygen delivery across the placenta.
Acid-Base Equilibrium↗
Effects of dehydroepiandrosterone sulfate on cellular calcium responsiveness and vascular contractility.
Dehydroepiandrosterone sulfate (DHEAS) is an endogenous steroid having a wide variety of biological effects, but its physiological role remains undefined. Since an age-related decline of DHEAS corresponds to the progressive onset of atherosclerosis, cardiovascular diseases, and overall mortality, we investigated a possible protective role of DHEAS in vascular disease by studying the effects of this hormone (10(-7) to 10(-5) mol/L) on cytosolic free calcium and contractility in different in vitro vascular tissue preparations. DHEAS produced a significant, dose-dependent relaxation of isolated helical strips of rat tail artery precontracted with KCl (60 mmol/L) (89.7 +/- 18.7%, P < .01), arginine vasopressin (3 nmol/L) (27.3 +/- 7.1%, P < .01), and norepinephrine (0.1 mumol/L) (49.2 +/- 18.2%, P < .01). In isolated vascular smooth muscle cells DHEAS reversibly inhibited KCl (30 mmol/L)-induced elevations of cytosolic free calcium to 69.8 +/- 8.4% and 43.8 +/- 7.4% of the control response at 5 x 10(-7) and 5 x 10(-6) mol/L, respectively (P < .05 at both doses). These results provide evidence of a direct vascular action of DHEAS, in doses reflecting circulating levels in vivo, and suggest the possibility that these effects are mediated by modulation of intracellular calcium metabolism. We hypothesize that physiologically, DHEAS may serve to buffer vascular responsiveness to a wide variety of depolarizing and constrictor hormonal stimuli.
Analysis of Variance↗
Glucose-induced alterations of cytosolic free calcium in cultured rat tail artery vascular smooth muscle cells.
We have previously suggested that hyperglycemia per se may contribute to diabetic hypertensive and vascular disease by altering cellular ion content. To more directly investigate the potential role of glucose in this process, we measured cytosolic free calcium in primary cultures of vascular smooth muscle cells isolated from Sprague-Dawley rat tail artery before and after incubation with 5 (basal), 10, 15, and 20 mM glucose. Glucose significantly elevated cytosolic free calcium in a dose- and time-dependent manner, from 110.0 +/- 5.4 to 124.5 +/- 9.0, 192.7 +/- 20.4, and 228.4 +/- 21.9 nM at 5, 10, 15, and 20 mM glucose concentrations, respectively. This glucose-induced cytosolic free calcium elevation was also specific, no change being observed after incubation with equivalent concentrations of L-glucose or mannitol. This glucose effect was also dependent on extracellular calcium and pH, since these calcium changes were inhibited in an acidotic or a calcium-free medium, or by the competitive calcium antagonist lanthanum. We conclude that ambient glucose concentrations within clinically observed limits may alter cellular calcium ion homeostasis in vascular smooth muscle cells. We suggest that these cellular ionic effects of hyperglycemia may underlie the predisposition to hypertension and vascular diseases among diabetic subjects and/or those with impaired glucose tolerance.
Animals↗