Biomedical subjects

M B Zemel

Publications and source records attributed to M B Zemel.

At least 73 records · Page 4Linked to original sources

PubMed1990

Effects of normal pregnancy on cellular cation metabolism and peripheral vascular resistance.

Normal pregnancy is associated with a poorly understood loss of vascular responsiveness to the pressor effects of infused angiotensin II. Since cellular cation metabolism appears to be a critical determinant of basal vascular tone and vascular reactivity, we have evaluated platelet ionized calcium, erythrocyte sodium, calcium and magnesium levels, and erythrocyte Ca-ATPase and Na/K ATPase activity in 15 normal black pregnant women (37.5 +/- 0.6 weeks gestation) and 10 normal age-matched nonpregnant black women. Plasma levels of factors potentially affecting vascular reactivity (endoxin, renin activity (PRA), and atrial natriuretic peptide (ANP] were measured by RIA and peripheral vascular resistance by biolectrical impedance. Peripheral vascular resistance was almost twice as high (P less than .003) in the normal group as in the pregnant women. Intracellular calcium concentrations were not significantly different in erythrocytes or platelets of the two groups. Although erythrocyte membrane Ca-ATPase was similar, Na/K ATPase activity was significantly higher in the pregnant subjects than in the nonpregnant controls, and intracellular sodium was lower. All three measured plasma factors, ANP, endoxin and PRA, were significantly elevated in the pregnant women. Our results suggest that the decrease in peripheral vascular resistance seen in normal pregnancy is probably not the result of alterations in cellular cation concentrations and/or cell membrane pump activity. However, the significant correlation between vascular reactivity and circulating ANP indicates this potent vasodilator may play a role in the observed decrease in peripheral vascular resistance associated with pregnancy.

Adult↗

PubMed1990

Clinical implications of hypertension in the diabetic patient.

We note that diabetes mellitus and hypertension coexist at a greater rate than would be indicated by chance. The combination of these two chronic disorders increases the risk of and mortality from such conditions as peripheral vascular disease, stroke, and nephropathy. Despite the importance of high blood pressure in diabetes, the underlying physiological mechanisms in this combined condition are poorly understood. This review explores the epidemiology, cardiovascular risks, pathophysiology and evaluation of this condition as well as outlining a general approach to treatment in the hypertensive diabetic.

Cardiovascular Diseases↗

PubMed1990

Dietary calcium induces regression of left ventricular hypertrophy in hypertensive non-insulin-dependent diabetic blacks.

Recent data from this laboratory indicate that dietary calcium supplementation causes reduced intracellular calcium in type II diabetic hypertensives. Consequently, we have assessed the effects of calcium supplementation on forearm blood flow (FBF) and vascular resistance (FVR) and left ventricular mass (LVM) in seven type II diabetic hypertensive black men with left ventricular hypertrophy (LVH) maintained off antihypertensive treatment for four weeks and then supplemented with 600 mg calcium per day for three months. A comparable group of black diabetic hypertensive patients treated with atenolol (50 mg) served as controls. LVM was determined by M-mode echocardiography and FBF and FVR by electrical impedance plethysmography at the end of the four week baseline and the 12 week supplementation periods. Calcium supplementation resulted in a decrease (P less than .05) in mean arterial pressure (from 121 +/- 4 to 114 +/- 3 mm Hg) which was accompanied by an 18% increase in FBF and a 20% reduction in FVR (P less than .05). LVM decreased from 289 +/- 22 at baseline to 240 +/- 22 g at the end of the supplementation period (P less than .02) and there was a significant correlation between changes in FBF and LVM (r = 0.82). Left ventricular end diastolic dimension decreased by 11% (P less than .05). These data indicate that calcium supplementation sufficient to normalize dietary calcium in black hypertensive diabetic men significantly reduces vascular resistance and causes partial regression of LVH.

Black People↗

PubMed1990

Increased sodium-lithium countertransport in black non-insulin-dependent diabetic hypertensives.

Black hypertensive diabetics have been shown to exhibit elevated intracellular calcium which may stimulate Na/H antiport. Since Na/Li countertransport appears to be a functional mode of Na/H antiport, we measured erythrocyte Na/Li countertransport in nondiabetic normotensive and hypertensive blacks and whites and hypertensive non-insulin-dependent diabetic blacks. Na/Li countertransport was significantly lower in the blacks than in the whites (0.170 +/- 0.017 v 0.230 +/- 0.017 mmol/L/h, P less than .02), but there was no significant difference between the black hypertensives and normotensives. In contrast, black hypertensive diabetics exhibited a significant increase in Na/Li countertransport compared to normotensive and hypertensive nondiabetic blacks (0.252 +/- 0.032 v 0.170 +/- 0.017, P less than .02. Thus, these data indicate that the activity of this antiporter is elevated in black diabetics, possibly further contributing to the development of hypertension in this population.

Adult↗

PubMed1990

Sodium bicarbonate and sodium chloride: effects on blood pressure and electrolyte homeostasis in normal and hypertensive man.

To test the hypothesis that NaCl and NaHCO3 have divergent effects on blood pressure, we carried out a randomly allocated, placebo-controlled, crossover trial in 10 mildly hypertensive and 10 normal subjects. They ingested a fixed daily basal diet of 60 mmol sodium and chloride, 60 mmol potassium and 14 mmol calcium. After balance was achieved (4 days), the subjects were randomly assigned to drink 3 liters/day of a NaHCO3-containing mineral water (26.2 mmol/l sodium and 33.03 mmol/l HCO3) or a control solution containing equimolar amounts of cations as the chloride salt for 7 days (total daily sodium 138 mmol). All urine was collected. Blood pressure was determined by an automated device. One month later the opposite regimen was followed. NaCl did not influence blood pressure, whereas NaHCO3 decreased systolic blood pressure (by 5 mmHg) in the hypertensive subjects. Both regimens decreased plasma renin activity in the hypertensive subjects but did not consistently influence plasma aldosterone or catecholamines. However, urinary calcium excretion, which was greater in hypertensives than in normotensives, and greater in white than in black subjects, increased consistently with NaCl but not with NaHCO3. The excretion of urate was not influenced by the regimens; however, urate excretion was consistently greater in whites than in blacks. The data show that NaCl increases calcium excretion whereas NaHCO3 does not, even at modest levels of intake. NaCl and NaHCO3 may therefore differ in their effects on blood pressure.

Adult↗

PubMed1990

A comparison of the efficacy and safety of a beta-blocker, a calcium channel blocker, and a converting enzyme inhibitor in hypertensive blacks.

A double-blind, positively controlled, forced dose titration study comparing the efficacy and safety of atenolol, captopril, and verapamil sustained release as single agents in the treatment of black patients with mild to moderate hypertension (diastolic blood pressure, 95 to 114 mm Hg) was conducted. A total of 394 patients were randomized to one of the three therapies. Mean blood pressures during a 2- to 4-week placebo treatment period (baseline) ranged from 100.4 to 100.7 mm Hg diastolic and 151.7 to 152.5 mm Hg systolic for the three groups. Of the patients, 355 (of whom 345 had assessable data) completed the first treatment period, which consisted of therapy with either 50 mg/d of atenolol, 25 mg every 12 hours of captopril, or 240 mg/d of verapamil sustained release. During the second 4-week treatment period, which 319 patients completed (307 assessable), half of the patients had their antihypertensive medication increased and the other half continued the same dose. Goal blood pressure was defined as a supine diastolic pressure of less than 90 mm Hg or a 10-mm Hg or greater drop in supine diastolic blood pressure from pretreatment levels. Atenolol, captopril, and verapamil sustained release therapy was associated with goal blood pressure achievement during the first treatment period 55.1%, 43.8%, and 65.2% of the time, respectively, and during the second treatment period 59.6%, 57.1%, and 73.0% of the time. Side effects were minimal and comparable for all three drugs.

Adult↗

PubMed1989

Role of cellular calcium metabolism in abnormal glucose metabolism and diabetic hypertension.

The prevalence of hypertension in patients with non-insulin-dependent diabetes mellitus (NIDDM) is considerably higher than in the non-diabetic population. Insulin resistance may contribute to this increased prevalence. Abnormal cellular calcium (Ca2+) homeostasis may link insulin resistance and high blood pressure in patients with NIDDM. Observations of abnormal cellular Ca2+ homeostasis in animal models of NIDDM and obesity as well as in diabetic patients are consistent with this hypothesis. Abnormalities in cellular Ca2+ homeostasis are also found in hypertensive animals and humans. Alterations in cell membrane phospholipid content and distribution may be the primary cause of abnormal plasma membrane Ca2+ fluxes in patients with NIDDM and hypertension.

Animals↗

PubMed1989

Erythrocyte cation metabolism in preeclampsia.

To determine if there are abnormalities in cellular cation regulation in pregnancy-induced hypertension, erythrocyte intracellular levels of calcium, magnesium, sodium, and potassium and circulating parathyroid hormone and "endoxin" were examined in 13 women with pregnancy-induced hypertension and 34 control subjects matched for gestational age (greater than or equal to 35 weeks). Both endoxin and parathyroid hormone levels were higher in patients with pregnancy-induced hypertension than in control subjects (endoxin, 294 +/- 34 vs. 210 +/- 19 pg/ml, p less than 0.05; parathyroid hormone, 0.65 +/- 0.05 vs. 0.60 +/- 0.03 ng/ml); the increase was significant only for endoxin. Intracellular calcium was higher in the patients with pregnancy-induced hypertension (0.033 +/- 0.010 vs. 0.015 +/- 0.001 mEq/L, p less than 0.05, in the patients with pregnancy-induced hypertension and control patients, respectively) but intracellular sodium, potassium, and magnesium levels were not different. This intracellular calcium elevation may be caused directly by the increase in parathyroid hormone or indirectly by the observed elevation in endoxin. Our data indicate that the observed effect is specific because no changes in intracellular sodium, potassium, or magnesium levels were found.

Black People↗

PubMed1989

Magnesium potentiation of iron-transferrin binding.

The binding of iron to transferrin was studied by loading iron (III) onto apotransferrin in a chloride and a nitrilotriacetate form. When magnesium was added, a marked increase occurred in both the rate of iron binding and the maximum level of iron loaded on transferrin utilizing either iron salt. In the absence of magnesium the amount of iron required to achieve 50 percent saturation of the binding sites was 1.6 x 10(-4) M, whereas when magnesium was added, only about one-third as much iron (0.54 x 10(-4) M) was required. These data suggest an allosteric effect on transferrin by magnesium which potentiates iron (III) binding.

Apoproteins↗

PubMed1989

Saline infusion causes rapid increase in parathyroid hormone and intracellular calcium levels.

Previous data demonstrate that increasing dietary NaCl causes an increase in intracellular calcium, possibly due to elevations in parathyroid hormone (PTH). To ascertain whether NaCl can induce a rise in PTH and thereby raise intracellular calcium, five adult males were infused with normal saline, and plasma was analyzed for intact PTH and erythrocytes for intracellular calcium at 15-minute intervals. Saline infusion caused a significant increase in PTH within 15 minutes and in intracellular calcium within 30 minutes. To further demonstrate that PTH was directly responsible for the increased intracellular calcium, erythrocyte suspensions were incubated with PTH, and the PTH caused significant, sustained elevations in erythrocyte total intracellular calcium. These data indicate that NaCl-induced increases in vascular resistance may result, in part, from PTH-induced increases in intracellular calcium.

Adult↗

PubMed1989

Age-associated changes in parathyroid hormone in black males.

To examine changes in calcium metabolism related to aging in blacks and caucasians, we measured serum mid-molecule parathyroid hormone (PTH), total and ionised calcium in 83 black and 47 caucasian healthy males aged 31-77 yrs. Age and race were without effect on total or ionised calcium. PTH levels increased significantly (P less than 0.03) with age in black but not caucasian subjects. These results demonstrate an aging-associated increase in circulating PTH in blacks and are consistent with other data from our laboratory which suggest that PTH may be involved in the development of salt-sensitive hypertension in blacks.

Adult↗

PubMed1989

Calcium and hypertension.

A possible relationship between dietary calcium intake and blood pressure has been the focus of considerable recent observational and experimental research. To provide a current perspective, we have reviewed and summarized the epidemiologic data, evidence suggesting abnormalities in calcium metabolism in human hypertension, studies evaluating calcium supplementation in various hypertension populations, and data that may help elucidate possible blood pressure-lowering mechanisms of calcium supplementation. An important relationship between "calcium metabolism" and "salt-sensitivity" is emerging and appears to be providing insights into potential mechanisms that account for the antihypertensive properties of dietary calcium in certain individuals. More experimental work needs to be performed to further define the individuals with hypertension who demonstrate a blood pressure-lowering response to dietary calcium supplementation.

Animals↗

PubMed1988

Salt sensitivity and systemic hypertension in the elderly.

Aging in industrialized societies is accompanied by increases in the incidence and prevalence of hypertension, with a disproportionately greater increase occurring among aging blacks than among aging whites. This geriatric hypertension is generally of a salt-sensitive nature with a disproportionate frequency of isolated systolic hypertension. Although salt-taste acuity declines with age, salt sensitivity among the elderly does not appear to result from a compensatory increase in salt intake. Rather, age-related increases in salt sensitivity result, in part, from a reduced ability to appropriately excrete a salt load, which is due to a decline in renal function and to a reduced generation of natriuretic substances such as prostaglandin E2 and dopamine. Age-associated declines in the activity of membrane sodium/potassium-adenosine triphosphatase (Na/K-ATPase) may also contribute to geriatric hypertension because this results in increased intracellular sodium that may cause reduced sodium-calcium exchange and thereby increase intracellular calcium and vascular resistance. Reductions in cellular calcium efflux due to reduced calcium-ATPase activity may similarly cause an increase in intracellular calcium and vascular resistance. Increasing dietary calcium intake may represent an effective nonpharmacologic treatment for some salt-sensitive persons because it appears to reduce intracellular calcium by (1) suppressing parathyroid hormone-mediated calcium influx, (2) increasing Na/K-ATPase activity, and (3) reducing intravascular volume due to calcium-induced natriuresis.

Aged↗

PubMed1988

Hypertension and diabetes.

Diabetes mellitus and hypertension are both common diseases, especially with an increasingly aged population. Hypertension accelerates the development of diabetic retinopathy, nephropathy, and peripheral vascular disease in the diabetic patient. Diabetes represents a type of premature aging and hypertension in the diabetic patient is characterized by many of the same pathophysiologic properties seen in the elderly hypertensive patient.

Antihypertensive Agents↗

PubMed1988

Calcium utilization: effect of varying level and source of dietary protein.

Dietary protein exerts a significant calciuretic effect. A twofold increase in protein at constant levels of calcium and phosphorus intakes causes a 50% increase in urinary calcium. The protein-induced hypercalciuria results primarily from decreased fractional renal tubular reabsorption of calcium associated with catabolism of excess sulfur amino acids and the resultant urinary excretion of acid and sulfate. A protein-induced elevation in glomerular filtration rate also contributes to the calciuresis. Dietary phosphorus also modifies the calciuretic effect of proteins, as it increases renal tubular reabsorption of calcium and thereby exerts a hypocalciuretic effect. Consequently, a soy-based diet was able to maintain calcium balance at a calcium intake of 457 mg/day in spite of a protein intake of 90 g, presumably due to the lower level of sulfur amino acids in the soy diet and to the 1450 mg phosphorus which accompanied the soy protein.

Blood Pressure↗

PubMed1988

Reductions in total and extracellular water associated with calcium-induced natriuresis and the antihypertensive effect of calcium in blacks.

Previous data from this laboratory suggest that Ca-induced reductions in blood pressure may result in part from Ca-induced natriuresis and a possible reduction in intravascular volume. Consequently, the present study was conducted to directly determine the relative effects of dietary Ca and Na on total body water (TBW) and extracellular water (ECW) as measured by tetrapolar bioelectrical impedance and to determine the potential relationship of these changes to diet-induced changes in blood pressure. Eleven hypertensive black adults were maintained for 14 days on each of four diets that contained 356 mg Ca or 1,000 mg Ca, each at 1,000 or 4,000 mg Na in a repeated measures design. Increasing dietary Na at the low Ca intake caused significant increases in supine systolic and diastolic pressure, reduced plasma renin activity (PRA), significantly increased TBW, and caused a significant reduction in total body reactance indicating an increase in ECW. Adding supplementary Ca to the low Na diet was without significant effect on blood pressure, PRA, TBW, or electrical reactance. In contrast, adding Ca to the low Ca-high Na diet caused a significant natriuretic effect that was accompanied by significant increases in PRA and electrical reactance and significant reductions in blood pressure and TBW, to baseline (low Ca-low Na levels). Thus, these data indicate that the antihypertensive effect of calcium in salt-sensitive blacks may be attributable, in part, to Ca-induced natriuresis and an associated volume contraction.

Adult↗

PubMed1988

Erythrocyte cation metabolism in salt-sensitive hypertensive blacks as affected by dietary sodium and calcium.

The role of dietary salt and calcium on changes in cellular cation metabolism has been evaluated in 11 salt-sensitive hypertensive black adults maintained on the following four metabolic diets for 56 days, 14 days on each diet in a repeated measures format: 356 mg Ca-1000 mg sodium (NA); 356 mg Ca-4000 mg Na; 934 Ca-1000 mg Na; and 934 mg Ca-4000 mg Na. Increasing dietary Na at the lower Ca intake caused significant (P less than 0.05) increases in parathyroid hormone (PTH) and 24-hour cyclic AMP excretion that were associated with significant (P less than 0.01) increases in erythrocyte intracellular calcium (from 5.4 +/- 0.7 to 11.1 +/- 3.7 microM), Ca-ATPase (from 37.2 +/- 2.4 to 42.2 +/- 2.1 pmol/min/10(6) cells) and intracellular sodium (from 220.5 +/- 7.4 to 262.0 +/- 8.3 micrograms/mL) and decreases (P less than 0.05) in Na/K-ATPase (from 1.90 +/- 0.55 to 1.48 +/- 0.47 pmol/min/10(6) cells) and intracellular magnesium (Mg) (from 52.4 +/- 3.5 to 43.8 +/- 2.4 micrograms/mL). Adding calcium to this high sodium diet reversed these effects, whereas adding calcium to the low sodium diet was without significant effect. These results indicate that dietary salt causes increases in intracellular sodium and calcium and that the antihypertensive effect of dietary calcium in salt-sensitive individuals may be attributable in part to preventing this salt-induced elevation in intracellular calcium. This increase in intracellular calcium could be due to the observed increase in PTH levels or to the salt-induced reduction in intracellular magnesium that appears to suppress Na/K-ATPase and thereby increases intracellular sodium.

Adult↗

PubMed1988

Altered cation transport in non-insulin-dependent diabetic hypertension: effects of dietary calcium.

Erythrocyte cation transport and intracellular calcium in 15 black type II diabetic hypertensives were compared with 11 otherwise similar non-diabetic hypertensives and 16 normal black adults. The diabetic hypertensives were then randomized into either a placebo group or a calcium-supplemented (600 mg/day) group and studied again after 4 weeks. Na+,K+-ATPase activity was significantly lower in both groups of hypertensives than in the normotensives. In contrast, Ca-ATPase activity was similar among the non-diabetic hypertensive and normotensives but was markedly (approximately 60%) suppressed in the diabetics, while intracellular calcium was proportionally elevated. Calcium supplements significantly increased Ca-ATPase activity and reduced intracellular calcium and blood pressure compared with the placebo group. We conclude that type II diabetes is characterized by a defect in Ca-ATPase which may be responsible for increases in intracellular calcium and vascular resistance and which is partially corrected by dietary calcium supplementation.

Calcium↗