Michael B. Zemel

Salt sensitivity in blacks. Salt intake and natriuretic substances.

Accumulating evidence suggests that hypertension in blacks is manifested in part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ in their ability to generate known natriuretic substances. Fourteen normotensive and 11 hypertensive blacks were maintained on constant metabolic diets containing either 40 or 180 mmol of salt per day for 14 days each. During the last 4 days of each salt intake period, urine was collected for measurement of sodium, dopamine, and norepinephrine. On the last day of each 14-day dietary period, blood pressures were measured, blood was collected for measurement of plasma atrial natriuretic factor (ANF) and aldosterone, and urine was collected over 2 hours for measurement of prostaglandin E2 (PGE2). Both the normotensive and the hypertensive groups manifested salt sensitivity; then- mean arterial pressure rose by 7 ± 0.2 and 6 ± 0.2%, respectively, when salt intake was increased from 40 to 180 mmoJ/day. The hypertensive group exhibited decreased (p < 0.05) dopamme excretion as compared with the normotensive group for both dietary salt intakes. Plasma ANF levels increased (p < 0.05) in the hypertensive group, but not in the normotensive group, with increasing dietary salt. Plasma aldosterone and urinary norepinephrine and PGE2 were comparable in the two groups for both dietary salt Intakes. These data suggest that salt sensitivity is not unique to hypertensive blacks but occurs in normotensive blacks as well. Decreased renal production of dopamme may be a pathogenic factor in the development and maintenance of hypertension in blacks.

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.

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.

Evidence for synergism between chromium and nicotinic acid in the control of glucose tolerance in elderly humans

Impaired glucose tolerance results from Cr restriction in animals, and Cr supplementation improves glucose tolerance in diabetic animals. These effects are presumably due to the role of Cr in glucose tolerance factor (GTF), a complex of Cr and nicotinic acid believed to facilitate insulin binding. Humans, however, do not uniformly respond to Cr supplementation. The present study was designed to evaluate the possibility that the failure results from inadequate levels of dietary nicotinic acid to serve as substrate for GTF synthesis. Sixteen healthy elderly volunteers were divided into three groups and given either 200 micrograms Cr, 100 mg nicotinic acid, or 200 micrograms Cr + 100 mg nicotinic acid daily for 28 days and evaluated on days 0 and 28. Fasting glucose and glucose tolerance were unaffected by either chromium or nicotinic acid alone. In contrast, the combined chromium-nicotinic acid supplement caused a 15% decrease in a glucose area integrated total (p less than .025) and a 7% decrease in fasting glucose. None of the treatments exerted any effect on fasting or one-hour insulin levels. Thus, these data suggest that the inability to respond to chromium supplementation may result from suboptimal levels of dietary nicotinic acid.

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.

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.

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.

Role of Nutrition in Black Hypertension: Calcium and Other Dietary Factors

A number of studies have shown that, on average, blacks in the Western Hemisphere have higher blood pressure than blacks from sub-Sahara Africa (2,77,92,123). Considerable regional variations in blood pressure also exist among blacks in the Western Hemisphere (6,42,49,90). This geographical heterogeneity in the prevalence of hypertension in various black populations around the world suggests that environmental factors play a critical role in determining the prevalence of hypertension in blacks (90). The importance of environment in contributing to the prevalence of hypertension in blacks is reinforced by the observation that when rural Africans undergo changes to more urban, Western lifestyles and diets, blood pressure increases (2,23,90,93, see Chapter 7, this volume). The information in this chapter examines one important environmental factor, nutrition, and its role in contributing to high blood pressure in urbanized, Westernized blacks (Table 8.1).

Effects of magnesium supplementation on erythrocyte cation transport in diuretic-treated hypertensives

Abstract Magnesium (Mg) deficiency increases vascular resistance in rats, and limited evidence suggests that Mg supplementation may reduce blood pressure, possibly due to activation of Na/K-ATPase and/or reduction of intracellular calcium. Further, treatment with thiazide and loop diuretics results in Mg depletion which may adversely affect cellular cation metabolism. Consequently, the present study was conducted to determine if such diuretic-induced alterations are preventable by Mg supplementation. Eleven diuretic-treated hypertensive patients completed a double blind randomized study with a 2-week single blind placebo period followed by 12 weeks on either placebo ((n=5) or 40 mEq Mg as Mg-Aspartate-HCl (n=6), and blood was collected for determination of erythrocyte intracellular cation levels and membrane Na/K- and Ca-ATPase activity. Mg supplementation resulted in increases (p

Metal utilization from casein and soy based diets as affected by tripolyphosphate and hexametaphosphate

Abstract Rats were fed casein- or soy based diets, both either free of polyphosphates or with 0.5% tripolyphosphate or hexametaphosphate incorporated. Both polyphosphates increased zinc absorption and utilization from both diets; the greatest effect was exerted in the soy diet, where tripolyphosphate was more effective. Both polyphosphates enhanced the absorption and liver accumulation of iron, but tripolyphosphate depressed femur iron levels, especially in the soy-fed animals. Tripolyphosphate reduced calcium and mangesium bioavailability, and both polyphosphates decreased urinary calcium, magnesium and fluid excretion. These effects were most pronounced in the soy-tripolyphosphate group, where renal calcification was found, but disappeared in all groups by the end of 15 days.