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M B Zemel

Publications and source records attributed to M B Zemel.

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

Hypertension in young, healthy Zucker obese rats is not responsive to reduced salt intake.

Hypertension in insulin resistant states is, in part, salt and volume dependent. The Zucker obese rat, a model of hypertension associated with insulin resistance, has been shown to exhibit a pressor response to a fourfold increase in NaCl intake, from 1 to 4 g/100 g. However, it is not clear if blood pressure is responsive to less severe manipulations, or if a NaCl restricted diet results in a depressor effect comparable to the pressor effect of adding supplementary NaCl to a normal diet. Consequently, we have determined the effects of NaCl restriction on blood pressure in Zucker lean and obese rats. Twenty-four 6-wk-old female Zucker lean and obese rats were randomly assigned to either a normal diet (1 g/100 g NaCl) or a NaCl restricted (0.26 g/100 g) diet for 4 wk. Direct intra-arterial blood pressure was then measured in conscious, unrestrained animals via a femoral cannula connected to a low volume pressure transducer and physiological recorder. Animals fed both diets grew normally, and there was no effect of diet on either food consumption or growth rate. Blood pressure was significantly higher in the obese than the lean rats. However, reducing NaCl intake had no effect on blood pressure in either group. Heart rate was not significantly different among the 4 groups. These data demonstrate that moderate reductions in dietary NaCl intake are without effect on blood pressure in Zucker obese rats despite their pressor response to large quantities of NaCl.

Animals↗
PubMed1994

Effects of oral calcium and potassium on endothelium-dependent relaxation in hypertensive rats.

High oral potassium (K) decreases stroke incidence in aging high salt-fed stroke-prone spontaneously hypertensive rats (SHRSP). We have seen high oral Ca increase stroke incidence in aging high salt-fed SHRSP without increasing blood pressure (BP) but with signs of K wasting. Therefore, we sought to determine whether high oral Ca suppresses the previously reported oral K-related enhancement of arterial endothelium-dependent relaxation as seen in younger high salt-fed SHRSP before the appearance of strokes. Four groups of female SHRSP were fed high-salt diets containing either low (0.4%) or high (1.6%) K with low (0.4%) and high (1.6%) Ca from age 1 to 4 mos. High oral K decreased BP independent of Ca intake (P < 0.05). High oral Ca did not affect BP. In contrast to aging SHRSP, high oral Ca neither increased urinary excretion nor decreased plasma concentration of K in these young adult SHRSP. However, high (vs. low) oral K only significantly reduced the half-maximal effective dose for acetylcholine-induced relaxation of aortic rings from rats fed low (18 +/- 3 vs. 38 +/- 6 nM, P < 0.05) not high Ca (25 +/- 5 vs. 31 +/- 3 nM). Neither oral K nor Ca affected nitroprusside-induced relaxation. Thus high oral Ca by itself does not impair endothelium-dependent relaxation in young adult high salt-fed SHRSP, but yet it suppresses the enhancing effect of high oral K on such relaxation and does so without altering BP, K balance, or endothelium-independent relaxation.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1993

Carotid plaque associations among hypertensive patients.

OBJECTIVE: To assess the relationship between cardiovascular risk factors and carotid plaque. DESIGN: Hypertensive patients were screened for randomization into the Multicenter Isradipine Diuretic Atherosclerosis Study, a trial intended to determine if blood pressure control by isradipine as compared with hydrochlorothiazide will blunt the progression of carotid plaque (intima plus media thickness, 1.3 to 3.5 mm) in patients with serum cholesterol levels of less than 6.85 mmol/L (265 mg/dL) without insulin-dependent diabetes mellitus or estrogen therapy. Demographics of those who underwent B-mode ultrasound evaluations at common, bifurcation, and internal carotid artery sites to detect plaque were assessed from a southern and a northern site. SETTING: Participants were from ambulatory outpatient clinics associated with medical schools. PATIENTS: The initial screening included 1823 hypertensive volunteer patients who were between 40 and 83 years of age who had a diastolic pressure of 90 to 114 mm Hg (or < 90 mm Hg with treatment). OUTCOME MEASURES: Complete data were collected on the variables of age, cholesterol, cigarette smoking, race, gender, and the presence of carotid plaque in 1126 patients. RESULTS: All variables were significantly associated with carotid plaque (intima plus media thickness, > or = 1.3 mm). The adjusted percentage with plaque was 66.4% +/- 3.4% for blacks and 70.1% +/- 2.3% for whites at the southern site and 42.7% +/- 4.5% for blacks and 61.3% +/- 3.2% for whites at the northern site. The rate of plaque was 75.8% among cigarette smokers, despite a mildly elevated cholesterol level. CONCLUSIONS: Although these 1126 cases do not constitute a random sample of patients, these data suggest that there may be regional differences in racial tendencies toward plaque among blacks.

Aged↗
PubMed1993

Impaired recovery of vascular smooth muscle intracellular calcium following agonist stimulation in insulin resistant (Zucker obese) rats.

We have previously shown that insulin attenuates vasoconstrictor responses to pressor agonists and accelerates vascular smooth muscle cell (VSMC) Ca(2+)-ATPase mediated Ca2+ efflux and vascular relaxation. We have now sought to determine if VSMC from insulin resistant (Zucker Obese, ZO) rats manifest exaggerated [Ca2+]i responses to pressor agonists and impaired [Ca2+]i recovery (rate of [Ca2+]i return to baseline) compared to their lean controls (ZL). Thoracic aortae from ZO and ZL were enzymatically digested to release VSMC (n = 16 animals/group and 8 determinations/group). Freshly dispersed cells were washed, counted, and loaded with Fura-2-AM. The [Ca2+]i responses to and rate of recovery from angiotensin II (AII; 200 nmol/L) and arginine vasopressin (AVP; 10 mumol/L) were studied fluorometrically in stirred suspension (10(6) cells/mL). Peak [Ca2+]i responses to AVP were not significantly different in ZO v ZL, while responses to AII were higher in ZL ([Ca2+]i, 180 +/- 7 v 160 +/- 4% of baseline in ZL and ZO, P < .02). Since we have recently shown insulin to increase AII-releasable Ca2+ stores in sarcoplasmic reticulum, this increase in peak [Ca2+]i response to AII in ZL may reflect relative VSMC insulin resistance in ZO. Despite their increased peak AII response, ZL exhibited a more rapid recovery from both the AII-stimulated load (recovery rate, 66.1 +/- 8.9 v 42.1 +/- 9.0 nmol/L/min in ZL and ZO, P < .02) and the AVP-stimulated [Ca2+]i load (22.2 +/- 2.3 v 18.4 +/- 4.6 nmol/L/min).(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1993

Insulin increases vascular smooth muscle recovery from intracellular calcium loads.

Insulin has previously been shown to attenuate vasoconstrictor responses to pressor agonists and accelerate vascular smooth muscle relaxation and vascular smooth muscle Ca2+ efflux. To further determine the role of insulin in regulating vascular smooth muscle Ca2+, quiescent A7r5 cultured vascular smooth muscle cells and human vascular smooth muscle cells were incubated with or without 10(-7) or 10(-8) M insulin for 1 hour and then loaded with fura 2-AM; intracellular Ca2+ responses to and rates of recovery from angiotensin II (200 nM) and arginine vasopressin (AVP) (10 microM) were studied fluorometrically in stirred suspension. Insulin (10(-7) M) caused an increase in the peak intracellular Ca2+ response to angiotensin II (peak/baseline x 100 = 469 +/- 96 versus 288 +/- 74, P < .05) and a decrease in the peak Ca2+ response to vasopressin (288 +/- 50 versus 389 +/- 33, P < .025). However, insulin also caused a marked increase in the rate of intracellular Ca2+ recovery to baseline after stimulation with both angiotensin II (77.3 +/- 13.8 versus 30.6 +/- 6 nM/min, P < .03) and vasopressin (P < .05), such that the cumulative exposure to elevated intracellular Ca2+ after stimulation with either agonist (ie, area under the intracellular Ca2+ curve) was reduced with insulin treatment. Insulin (10(-8)) caused small but still significant effects on all parameters in the A7r5 cells. Insulin also caused comparable effects on Ca2+ recovery in the human cells but was without significant effect on peak Ca2+ responses to AVP.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗
PubMed1992

Insulin-stimulated vascular relaxation. Role of Ca(2+)-ATPase.

We have recently described defects in vascular smooth muscle Ca2+ transport in insulin-resistant states. Since insulin stimulates plasmalemmal Ca(2+)-ATPase activity in some tissues, loss of this stimulation in insulin resistance may result in reduced Ca2+ efflux, and, consequently, increased intracellular Ca2+ and vascular tone. Consequently, the present studies were conducted to determine the effects of insulin on vascular smooth muscle Ca2+ efflux and vascular relaxation following vasoconstriction, and to determine whether these effects are attributable to insulin stimulation of Ca(2+)-ATPase. Endothelium-denuded rat aortic strips were incubated for 1 h in the presence or absence of insulin (0.1 mU/mL), and 45Ca2+ efflux was measured. In some experiments, either a low Na+ (3 to 5 mmol/L) medium was used to inhibit Na+/Ca2+ exchange, vanadate (1 mmol/L) was added to inhibit Ca(2+)-ATPase activity, or the insulin level was varied (0.01 to 1.00 mU/mL) to establish dose dependence. To determine the effects of insulin on vascular relaxation, endothelial denuded aortic strips were suspended in a muscle bath and connected to an isometric force transducer. The strips were incubated with insulin (0.1 U/mL) or vehicle for 1 h, contracted with phenylephrine, and the rate of spontaneous relaxation following phenylephrine washout was measured. Insulin (0.1 mU/mL) stimulated both Ca2+ efflux (efflux rate constant = 0.288 +/- 0.038 v 0.361 +/- 0.036 min-1 in control and insulin-treated strips, respectively; P less than .005) and relaxation rate (3.97 +/- 0.35 v 4.63 +/- 0.31%/min; P less than .01), and both of these effects were inhibited by vanadate.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Hypertension in insulin-resistant Zucker obese rats is independent of sympathetic neural support.

We have previously reported that insulin-resistant Zucker obese rats exhibit hypertension associated with impaired vascular smooth muscle (VSM) Ca2+ transport and proposed that this results from failure of insulin to regulate VSM Ca2+ transport in insulin resistance. However, hypertension in insulin-resistant states is generally attributed to hyperinsulinemia, with a consequent stimulation of sympathetic neural activity. Accordingly, the present study was conducted to determine whether the hypertension observed in Zucker obese rats compared with their lean controls was dependent on either increased sympathetic neural activity or exaggerated vascular reactivity. Intra-arterial blood pressure responses to ganglionic blockade with Ecolid (chlorisondamine chloride) and to graded intravenous injections of angiotensin II and norepinephrine were compared in 6- to 8-wk-old male Zucker rats and their lean controls (n = 10/group). The obese rats exhibited significant hypertension before ganglionic blockade (P less than 0.001), and this difference was largely sustained during ganglionic blockade (P less than 0.005). Furthermore, the obese rats exhibited greater pressor sensitivity to both angiotensin II and to norepinephrine during ganglionic blockade (P less than 0.01). Thus enhanced pressor sensitivity, independent of sympathetic neural activity, appears to support hypertension in Zucker obese rats.

Angiotensin II↗
PubMed1991

Insulin attenuation of vasoconstrictor responses to phenylephrine in Zucker lean and obese rats.

Recent data from this laboratory indicate that insulin resistant obese Zucker rats exhibit hypertension associated with exaggerated in vitro vascular reactivity to phenylephrine, serotonin, and KCl, and we have found insulin to attenuate vascular reactivity responses to these agonists. Accordingly, in the present study we evaluated the possibility that exaggerated vascular reactivity responses in obese Zucker rats may result from insulin resistance and a consequent failure of insulin to attenuate vasoactive responses. Thoracic aortae were isolated from male 16 week old lean and obese Zucker rats, and replicate helical strips from each animal were suspended in a muscle bath under a resting tension of 1.4 g in the presence or absence of insulin (0.1 mU/mL) for 1 h. The insulin was then washed out, and vascular reactivity responses to phenylephrine were determined. The obese rats exhibited greater reactivity to phenylephrine (ED50:1.10 +/- 90 X 10(-8) v 7.57 +/- 0.88 X 10(-10) mol/L in lean and obese rats, respectively, P less than .025). Insulin caused a significant attenuation of the contractile response in both the lean and obese aortae. However, lean rats exhibited a markedly greater attenuation than the obese rats (46.0 +/- 17.0 v 17.8 +/- 7.5% attenuation in the lean and obese rats, respectively, P less than .01). These data suggest that increased vascular reactivity responses in obese Zucker rats may result from their insulin resistant state and, consequently, a diminished ability of insulin to attenuate vasoconstrictor responses.

Animals↗
PubMed1991

Human platelet calcium measurements. Methodological considerations and comparisons with calcium mobilization in vascular smooth muscle cells.

Platelets are used as models for vascular smooth muscle cells (VSMC) in evaluating intracellular calcium ([Ca2+]i) metabolism in humans. This study was designed to determine if agonist-induced increases in [Ca2+]i in platelets occur via release from intracellular stores as previously demonstrated for VSMC. Incubation of purified platelets loaded with fura-2-AM in media containing 1.5 mmol/L Ca2+ resulted in higher basal [Ca2+]i than platelets incubated in Ca(2+)-free media. In addition, vasopressin-induced platelet [Ca2+]i transients were almost completely blocked by Ca2+ channel blockers. Thus, in contrast to VSMC, the transmembranous flux of extracellular Ca2+ is the major mechanism in vasopressin-induced increases in platelet [Ca2+]i, while mobilization of intracellular Ca2+ stores is only minimally involved.

Arginine Vasopressin↗
PubMed1991

Calcium metabolism and dietary calcium in salt sensitive hypertension.

Evidence has accumulated over the past decade that suggests a relationship between low calcium intake, abnormalities in cation metabolism and hypertension in certain segments of the essential hypertension population. This evidence has been developed from epidemiological data, calcium intervention trials and observations related to biochemical alterations suggestive of a calcium deficiency in certain patients with hypertension and in animal models of essential hypertension. It is becoming increasingly evident that salt sensitive individuals are especially likely to be characterized by abnormalities of calcium metabolism and blood pressure responses to dietary calcium. In this review the role of calcium in the regulation of blood pressure is examined with an emphasis on epidemiological, biochemical, hemodynamic and dietary intervention data in the salt sensitive hypertensive patient.

Blood Pressure↗
PubMed1991

Insulin resistance, carbohydrate metabolism, and hypertension.

Hypertension and diabetes are common diseases in Westernized civilizations, and in the United States, the frequency of both diseases is increasing as the society ages. Factors contributing to the high prevalence and increasing frequency of these diseases include obesity, hyperinsulinemia and insulin resistance, genetic factors, and abnormal cellular handling of calcium and other cations. Obesity is a strong early predictor for the development of hypertension as a person progresses from childhood into adult life. Important factors contributing to obesity-related hypertension likely include enhanced sympathetic nervous system activity and insulin resistance and hyperinsulinemia. Recent evidence has also shown that many nonobese adults with untreated hypertension have insulin resistance and hyperinsulinemia. This observation strongly suggests that the disease called "hypertension" is characterized by fundamental metabolic abnormalities as well as by hemodynamic abnormalities. Recent observations have shown that impaired cellular responses to insulin are associated with increased vascular smooth muscle contraction. Insulin appears to attenuate the vascular response to both receptor-mediated and voltage-mediated calcium-induced contractions. Thus, insulin resistance, and the resultant reduction in the normal attenuating effect of insulin on vascular smooth muscle responses, appear to be associated with abnormal vascular smooth muscle handling of calcium and with exaggerated vascular contraction.

Animals↗
PubMed1991

Effects of dietary calcium on blood pressure, vascular reactivity and vascular smooth muscle calcium efflux rate in Zucker rats.

Previous data from this laboratory indicate that hypertension in insulin resistant Zucker obese rats is accompanied by an impairment in vascular smooth muscle Ca2+ efflux. Since insulin resistant states are also generally salt-sensitive and dietary Ca2+ reduces blood pressure in some salt-sensitive states, we evaluated the effects of dietary Ca2+ on blood pressure and vascular reactivity and examined whether these effects are due to increased vascular smooth muscle Ca2+ efflux. We assigned 16 obese and 16 lean rats to a normal (0.5%) or high (1.5%) Ca2+ diet for 28 days, following which intraarterial blood pressure and in vitro vascular smooth muscle 45Ca efflux and vascular reactivity responses to phenylephrine and serotonin were measured. Blood pressure was elevated in the obese rats on both diets (P less than 0.2), and the high calcium diet lowered both systolic and diastolic pressure in both the lean and obese rats (P less than 0.5). Vascular reactivity was higher in the obese rats (P less than 0.2), but dietary Ca2+ exerted opposite effects on vascular reactivity to the agonists. High Ca2+ reduced sensitivity to serotonin in the obese rats by 54% (P less than .05) without affecting sensitivity in the lean rats. In contrast, the high Ca2+ diet increased sensitivity to phenylephrine by 31% in both groups (P less than .01). 45Ca efflux was lower in the obese rats compared to the lean rats (P less than .05), and the high Ca2+ diet increased this rate by 23% in the lean, but not the obese, rats (P less than .05).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Insulin attenuates vasopressin-induced calcium transients and a voltage-dependent calcium response in rat vascular smooth muscle cells.

Insulin attenuates the contractile responses of vascular smooth muscle (VSM) to various agonists. Insulinopenic and insulin-resistant rats lack this normal attenuation of vascular contractile responses. To study this attenuating mechanism, the effects of insulin on calcium (Ca2+) responses of cultured VSM cells (a7r5) to arginine vasopressin (AVP) and membrane potential were investigated. Insulin (1 and 100 mU/ml) shifted AVP dose-response curves to the right, reducing relative potency of AVP by 16-fold and 220-fold, respectively. Responses to AVP were significantly attenuated within 30 min of insulin application. The AVP-elicited rise in [Ca2+]i was partially dependent upon extracellular Ca2+. AVP-elicited inward current was reduced by 90 min of insulin treatment (100 mU/ml), from a peak current of -103 +/- 27 pA (normal) to -37 +/- 15 pA (insulin treated). Peak voltage-dependent Ca(2+)-dependent inward current was unaffected by insulin; however, the current-voltage curve was shifted 16 +/-3 mV to the right by insulin. Thus, insulin may reduce VSM contractile responses by attenuating agonist-mediated rises in [Ca2+]i mediated, in part, by reductions in Ca2+ influx through both receptor- and voltage-operated channels.

Animals↗
PubMed1990

Altered platelet calcium metabolism as an early predictor of increased peripheral vascular resistance and preeclampsia in urban black women.

BACKGROUND: Although preeclampsia is an important and relatively common medical problem, its pathophysiology remains unresolved and the search for a biochemical marker that precedes the hemodynamic abnormalities of preeclampsia continues. We designed a study to investigate the hemodynamic changes that characterize preeclampsia and to evaluate the metabolism of platelet intracellular calcium as a possible predictor of the development of preeclampsia. METHODS: Hemodynamic measurements and spectrofluorometric determinations of the levels of intracellular calcium in platelets in the basal state and after stimulation with an agonist were performed in 48 nulliparous black women during each trimester of pregnancy. The data on the 14 women (29 percent) in whom preeclampsia developed were then compared with the data on the other 34, who served as normotensive controls. RESULTS: There was no significant difference between the two groups in the basal levels of intracellular calcium at any time. In contrast, the levels measured after arginine vasopressin was administered during the first trimester indicated an exaggerated response in the group with preeclampsia as compared with the control group (1494 +/- 388 [+/- SEM] percent vs. 545 +/- 55 percent of base line; P less than 0.0002), which was sustained through the second and third trimesters. All but three of the women with preeclampsia had responses higher than the highest response among the controls. Platelet intracellular calcium responses to arginine vasopressin during the first trimester were a sensitive predictor of the subsequent development of preeclampsia (P less than 0.00009). Although vascular resistance was similar in the two groups during the first trimester, it subsequently decreased in the control group (P less than 0.02) but not in the group with preeclampsia. CONCLUSIONS: Our findings indicate that preeclampsia is characterized by the absence of the normal pregnancy-related decrease in vascular resistance, which is preceded in most instances by an exaggerated response of platelet intracellular calcium to arginine vasopressin early in pregnancy. We therefore propose that an increase in the sensitivity of platelet calcium to arginine vasopressin can be used as an early predictor of subsequent preeclampsia.

Adolescent↗
PubMed1990

Impaired calcium metabolism associated with hypertension in Zucker obese rats.

Recent data from our laboratory indicate that reduced membrane Ca-adenosine triphosphatase (ATPase) activity in non-insulin-dependent diabetics may be responsible for increases in intracellular calcium and, consequently, for elevated vascular resistance. Since obesity is frequently associated with hypertension, even before the development of overt diabetes, we evaluated blood pressure and erythrocyte cation levels and membrane Na/K-ATPase and Ca-ATPase in Zucker obese rats and their lean controls (n = 10 per group). Intra-arterial blood pressure, determined via a femoral cannula, demonstrated elevated systolic and diastolic pressure in the obese rats (P less than .05). There were no significant differences in Na/K-ATPase between groups, but there was a decrease in Ca-ATPase (P less than .01) in the obese rats and an increase in tissue and cellular calcium content (P less than .05). These data demonstrate a specific impairment in membrane Ca-ATPase activity in obese rats they may have caused the observed increase in cellular calcium and, consequently, increased blood pressure. These phenomena may result from impaired insulin activation of membrane Ca-ATPase in these insulin-resistant animals.

Animals↗
PubMed1990

Abnormal Ca2(+)-ATPase activity in erythrocytes of non-insulin-dependent diabetic rats.

Non-insulin-dependent diabetic (NIDD) rats have an increased Ca2(+)-ATPase activity in their kidney basolateral membranes. We find that a similar increased activity occurs in erythrocytes of the NIDD animals. This alteration in membrane ATPase activity appears to be specific for the Ca2(+)-ATPase as (Na(+) + K+) and Mg2(+)-ATPase and Na, K and Mg concentrations in the erythrocyte were not affected by the diabetic condition in these animals. Thus, abnormalities in membrane Ca2(+)-ATPase activity in the NIDD rats are not restricted to one tissue and appear to be a generalized pathology in the NIDD animals.

Animals↗
PubMed1990

Metabolic and hemodynamic effects of magnesium supplementation in patients with essential hypertension.

The effect of magnesium supplementation on blood pressure, erythrocyte cation metabolism, and serum lipids was evaluated in 13 patients with mild hypertension. After randomization and a 3-wk placebo run-in period, seven patients received 40 mmol Mg aspartate (20 mmol elemental Mg twice daily) and six received placebo for 3 mo. In comparison with placebo treatment, magnesium aspartate therapy had no effect on blood pressure, lipid concentrations, or erythrocyte cation metabolism. These results demonstrate that in magnesium-repleted hypertensive subjects, magnesium supplementation does not affect blood pressure or lipids probably because magnesium has no effect on cellular cation metabolism in magnesium-replete individuals.

Adult↗