Recent data from this laboratory demonstrate that increasing adipocyte intracellular Ca(2+) results in a coordinated stimulation of lipogenesis and inhibition of lipolysis. We have also noted that increasing dietary calcium of obese patients for 1 year resulted in a 4.9 kg loss of body fat (P<0.01). Accordingly, we tested the possibility that calcitrophic hormones may act on adipocytes to increase Ca(2+) and lipid metabolism by measuring the effects of 1, 25-(OH)(2)-D in primary cultures of human adipocytes, and found significant, sustained increases in intracellular Ca(2+) and a corresponding marked inhibition of lipolysis (EC(50) approximately 50 pM; P<0.001), suggesting that dietary calcium could reduce adipocyte mass by suppressing 1,25-(OH)(2)-D. To test this hypothesis, we placed transgenic mice expressing the agouti gene specifically in adipocytes on a low (0.4%) Ca/high fat/high sucrose diet either unsupplemented or with 25 or 50% of the protein replaced by non-fat dry milk or supplemented to 1.2% Ca with CaCO(3) for 6 wk. Weight gain and fat pad mass were reduced by 26-39% by the three high calcium diets (P<0.001). The high calcium diets exerted a corresponding 51% inhibition of adipocyte fatty acid synthase expression and activity (P<0.002) and stimulation of lipolysis by 3. 4- to 5.2-fold (P<0.015). This concept of calcium modulation of adiposity was further evaluated epidemiologically in the NHANES III data set. After controlling for energy intake, relative risk of being in the highest quartile of body fat was set to 1.00 for the lowest quartile of Ca intake and was reduced to 0.75, 0.40, and 0.16 for the second, third, and fourth quartiles, respectively, of calcium intake for women (n=380;P<0.0009); a similar inverse relationship was also noted in men (n=7114; P<0.0006). Thus, increasing dietary calcium suppresses adipocyte intracellular Ca(2+) and thereby modulates energy metabolism and attenuates obesity risk.

SUMMARY Accumulating evidence suggests that hypertension hi blacks is manifested hi part by impaired renal excretion of salt. Consequently, this study was performed to determine if hypertensive and normotensive black subjects differ hi 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 E 2 (PGE 2 ). 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 PGE 2 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 hi normotensive blacks as well. Decreased renal production of dopamme may be a pathogenic factor hi the development and maintenance of hypertension in blacks. compared with hypertension in whites, is characterized by a higher incidence of salt sensitivity '-4 in spite of the apparent lack of differences in sodium and salt intakes between the two populations. 5 The mechanisms involved in the relatively high incidence of salt-sensitive hypertension in blacks are poorly understood. However, an impaired natriuretic response to a salt load in hypertensive blacks could result from a reduced ability to generate natriuretic substances such as dopamine (DA), prostaglandin E? (PGE2), and atrial natriuretic factor (ANF).There is a considerable body of evidence suggesting a relationship between renal production of DA and the ability of the kidney to excrete a salt load. 6 -21 Enhanced dietary salt intake or infusion of saline results in an increase in urinary DA excretion and a decrease in norepinephrine excretion. 13 -22 That the dietary salt or saline-mediated natriuresis is causally linked to renal DA excretion is supported by the observation that administration of carbidopa, the peripheral inhibitor of the enzyme dopa decarboxylase, prevents the increases in urinary sodium in response to dietary salt 23 and saline infusion. 14 -15 However, there is evidence that salt loading does not appropriately increase urinary DA excretion in hypertensive patients, 24 -M suggesting that decreased renal DA production in response to...

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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.

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.