Dietary sodium intake and age in spontaneously hypertensive rats: effects on blood pressure and sympathetic activity

Spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) were placed on sodium restricted diets (9 and 17 mumol/g) or on a regular sodium diet (101 mumol/g) at 2, 4, 7, or 10 weeks of age, and continued until 16 weeks of age. Severe sodium restriction (9 mumol/g) initiated at 2 or 4 weeks of age prevented hypertension development in SHR and severely retarded growth. Hypertension development was attenuated when 9 mumol/g was initiated at 7 weeks of age, and was not affected when started at 10 weeks of age. Mean arterial pressure (MAP) in WKY receiving 9 mumol Na/g initiated at 2 and 4 weeks of age was below normal, but was not affected when this diet was given at 7 or 10 weeks of age. Less severe sodium restriction (17 mumol Na/g) resulted in a reduction in hypertension development when initiated at 2, 4, and 7 weeks of age, but not at 10 weeks of age. MAP was normal in WKY receiving 17 mumol Na/g at all ages of diet initiation. When the 9 or 17 mumol Na/g diet were initiated at 2, 4, and 7 weeks of age, the response of blood pressure to hexamethonium administration was blunted in SHR relative to both WKY receiving the same diet, and to control SHR receiving 101 mumol Na/g. We conclude that both WKY and SHR require a minimum amount of dietary sodium for normal growth and for the achievement of normal BP in WKY, and hypertension in SHR. This sodium requirement decreases with age. SHR and WKY exhibit similar sensitivities to sodium intake with respect to body weight, but the effects on BP are more pronounced in SHR. The BP lowering effects of dietary sodium restriction may be due to a blunting of the pressor effectiveness of the sympathetic nervous system.     

Statistical issues in a metaregression analysis of randomized trials: impact on the dietary sodium intake and blood pressure relationship

In a meta-analysis of randomized trials of the effects of dietary sodium interventions on blood pressure, we found substantial heterogeneity among the studies. We were interested in evaluating whether measurement error, known to be a problem for dietary sodium measures, publication bias, or confounding factors could be responsible for the heterogeneity. A measurement error correction was developed that corrects both the slope and the intercept and takes into account the sample size of each study and the number of measurements taken on an individual. The measurement error correction had a minimal effect on the estimates, although it performed well in simulated data. A smoothed scatter plot was used to assess publication bias. Metaregressions provide a convenient way to jointly assess the effects of several factors, but care must be taken to fit an appropriate model.     

The effects of protein intake on blood pressure and cardiovascular disease

PURPOSE OF REVIEW: Investigators, especially those from western countries, have commonly assumed that there is either no association or a direct association of protein intake with elevated blood pressure and atherosclerosis. In contrast, recent observational studies and clinical trials have suggested that increased protein intake, particularly protein from plant sources, might actually reduce blood pressure and prevent cardiovascular disease. RECENT FINDINGS: In epidemiological studies, an increased intake of protein has been associated with lower blood pressure and an attenuated increase in blood pressure over time. Furthermore, such studies also suggest that the beneficial effects of increased protein intake result from an increased consumption of protein from plant rather than animal sources. In several predominantly small trials, an increased intake of soy protein lowered blood pressure. With respect to clinical outcomes, reports from large cohort studies suggest that increased protein intake is associated with a reduced risk of ischemic heart disease and perhaps intraparenchymal hemorrhage. In other reports, a higher protein intake is one characteristic of a dietary pattern associated with a reduced risk of ischemic heart disease. The mechanisms by which protein could exert its beneficial effects include an increased intake of biologically active amino acids, peptides, or highly correlated nutrients. SUMMARY: Recent evidence suggests that an increased intake of protein, particularly plant protein, may lower blood pressure and reduce the risk of cardiovascular disease. However, the data are not sufficiently compelling to advocate an increased consumption of protein.     

Differential effects of the changes of LDL cholesterol and systolic blood pressure on the risk of carotid artery atherosclerosis

ABSTRACT: BACKGROUND: The effects of baseline and changes in blood pressure and low density lipoprotein (LDL) cholesterol on the carotid intima media thickness (IMT) have not been well documented. METHODS: A total of 2572 adults (mean age 53.8 years, 54.6% women) in a Taiwanese community undertook three blood pressure and LDL cholesterol examinations over 6 years. Latent growth curve modeling was used to investigate the effects of baseline and change in blood pressure and LDL cholesterol on IMT. RESULTS: Greater baseline LDL and blood pressure were associated with an increase in IMT (0.005 +/- 0.002 mm per 1 mg/dL [p = 0.006] and 0.041 +/- 0.004 mm mmHg [p <0.0001], respectively. Change in blood pressure was associated with a significant increase in IMT (0.047+/-0.016, P = 0.004), whilst the association between change in LDL and change in IMT was not statistically significant (0.008+/-0.006, P = 0.20). CONCLUSIONS: Carotid IMT was associated with baseline blood pressure and LDL cholesterol, yet only changes of blood pressure, not LDL cholesterol, were related to carotid IMT during the 6- year observation.     

Influence of dietary linoleic acid on leucocyte sodium transport and blood pressure.

In a randomised double blind study to determine whether an increase in the polyunsaturated fat linoleic acid might influence leucocyte membrane sodium transport 22 normotensive volunteers received an oral supplement of linoleic acid or placebo daily for four weeks. Mean total sodium efflux rose significantly during supplementation with linoleic acid compared with placebo. In addition, all components of lying and standing blood pressure fell, though only the fall in supine systolic pressure was significant. Dietary supplementation with linoleic acid may alter ion fluxes across the cell membrane, presumably through changes in its physicochemical structure. In addition, the change in fat intake may lower blood pressure, though to only a very modest extent.     

Renal denervation chronically lowers arterial pressure independent of dietary sodium intake in normal rats

The present study was designed to test the hypothesis that renal nerves chronically modulate arterial pressure (AP) under basal conditions and during changes in dietary salt intake. To test this hypothesis, continuous telemetric recording of AP in intact (sham) and renal denervated (RDNX) Sprague-Dawley rats was performed and the effect of increasing and decreasing dietary salt intake on AP was determined. In protocol 1, 24-h AP, sodium, and water balances were measured in RDNX (n = 11) and sham (n = 9) rats during 5 days of normal (0.4% NaCl) and 10 days of high (4.0% NaCl) salt intake, followed by a 3-day recovery period (0.4% NaCl). Protocol 2 was similar with the exception that salt intake was decreased to 0.04% NaCl for 10 days after the 5-day period of normal salt (0.04% NaCl) intake (RDNX; n = 6, sham; n = 5). In protocol 1, AP was lower in RDNX (91 +/- 1 mmHg) compared with sham (101 +/- 2 mmHg) rats during the 5-day 0.4% NaCl control period. During the 10 days of high salt intake, AP increased <5 mmHg in both groups so that the difference between sham and RDNX rats remained constant. In protocol 2, AP was also lower in RDNX (93 +/- 2 mmHg) compared with sham (105 +/- 4 mmHg) rats during the 5-day 0.4% NaCl control period, and AP did not change in response to 10 days of a low-salt diet in either group. Overall, there were no between-group differences in sodium or water balance in either protocol. We conclude that renal nerves support basal levels of AP, irrespective of dietary sodium intake in normal rats.     

Effect of dietary sodium on estrogen regulation of blood pressure in Dahl salt-sensitive rats

The effects of high-sodium (HS) and normal-sodium (NS) diets on ovarian hormone modulation of mean arterial pressure (MAP) were examined in Dahl salt-resistant (DR) and salt-sensitive (DS) rats. Ovariectomy increased MAP (OVX-Sham) to a greater extent in DS rats maintained for 2 wk on a HS (22 mmHg) compared with a NS (6 mmHg) diet. Ovariectomy had no effect on MAP in DR rats on NS but did increase MAP in rats on HS (10 mmHg) diets. On HS diets, glomerular filtration rate (GFR) was 36% less in the DS-Sham than DR-Sham animals; ovariectomy increased GFR in both strains by 1.4-1.5-fold; glomerular angiotensin II type 1 receptor (AT(1)R) densities were 1.6-fold higher in the DS-Sham than in the DR-Sham group; ovariectomy increased glomerular AT(1)R densities by 1.3-fold in DR rats but had no effect in DS rats; 17beta-estradiol (E(2)) downregulated adrenal AT(1)R densities in both strains on either diet; ovariectomy reduced estrogen receptor-alpha (ER-alpha) protein expression in the renal cortex by 40-50% although renal ER-alpha expression was 34% lower in DS than in DR rats. These observed effects of gonadectomy were prevented by E(2) treatment, suggesting that E(2) deficiency mediates the effects of ovariectomy on MAP, GFR, AT(1)R densities, and renal ER-alpha protein expression. In conclusion, ovariectomy-induced increases in MAP are augmented by HS diet in both strains, and this effect is not mediated by a reduction in GFR. Aberrant renal AT(1)R regulation and reduced renal ER-alpha expression are potential contributors to the hypertensive effects of E(2) deficiency in DS rats. These findings have implications for women with salt-sensitive hypertension and women who are E(2) deficient, such as postmenopausal women.     

Relation between arterial pressure,dietary sodium intake,and renin system in essential hypertension.

Forty-one patients with mild essential hypertension, 36 patients with severe hypertension, and 28 normotensive subjects were studied on a high sodium intake of 350 mmol/day for five days and low sodium intake of 10 mmol/day for five days. The fall in mean arterial pressure on changing from the high-sodium to the low-sodium diet was 0.7 +/- 1.7 mm Hg in normotensive subjects, 8 +/- 1.4 mm Hg in patients with mild hypertension, and 14.5 +/- 1.4 mm Hg in patients with severe hypertension. The fall in blood pressure was not correlated with age. Highly significant correlations were obtained for all subjects between the ratio of the fall in mean arterial pressure to the fall in urinary sodium excretion on changing from a high- to a low-sodium diet and (a) the level of supine blood pressure on normal diet, (b) the rise in plasma renin activity, and (c) the rise in plasma aldosterone. In patients with essential hypertension the blood pressure is sensitive to alterations in sodium intake. This may be partly due to some change either produced by or associated directly with the hypertension. A decreased responsiveness of the renin-angiotensin-aldosterone system shown in the patients with essential hypertension could partly account for the results.     

Protective effect of dietary tomato against endothelial dysfunction in hypercholesterolemic mice

The effects of dietary ingestion of tomato were studied in mice that had been made hypercholesterolemic by feeding atherogenic diets. Mice which had been fed on the atherogenic diet without tomato for 4 months had significantly increased plasma lipid peroxide, and the vaso-relaxing activity in the aorta induced by acetylcholine (ACh) was harmed when compared with mice fed on a common commercial diet. On the other hand, mice which had been fed on the atherogenic diet containing 20% (w/w) lyophilized powder of tomato showed less increase in the plasma lipid peroxide level, and ACh-induced vaso-relaxation was maintained at the same level as that in normal mice. These results indicate that tomato has a preventive effect on atherosclerosis by protecting plasma lipids from oxidation.     

Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.     

Effects of dietary intake of trace metals on tissue contents of sodium and calcium in mice (Mus musculus)

Mice were given either cadmium (Cd), copper (Cu) or zinc (Zn) ad lib, and levels of the metals in the heart, kidneys and liver were measured together with organ contents of sodium (Na) and calcium (Ca). The contents of Cd increased more than 100-fold in all organs, whereas Zn increased by a factor of 2-4. Copper accumulated only in the liver. Cadmium exposure caused the Na and Ca contents in the kidneys to increase by a factor of 2-3, but caused a statistically significant reduction in the Na content of the liver. Cadmium also caused a reduction in the Ca content of the heart. Copper caused a statistically significant doubling of the Na content in the heart, but a significant reduction in the Ca content in this organ. Zinc caused a reduction in the Ca content of the heart. However, the mechanisms behind these effects are not clear. The accumulation of Cd in the kidneys and heart was associated with a gradual change in the Na and Ca levels in these organs, but trace metal accumulation was not associated with any conspicuous changes in the Na or Ca contents in any other organ. Copper was not accumulated in heart, but Cu intake still had marked effects on the Na and Ca contents in this organ. Since the tissue contents of Na and Ca are likely to be physiologically important, these ions may have potential as biomarkers for toxic stress. Since the effects of Cd and Cu differed markedly, the tissue contents of Na and Ca may also be used in a trace metal-specific system of fingerprint biomarkers.     

Blood pressure and endocrine responses of healthy subjects in cold pressor test after acutely increased dietary sodium intake

The objective of the study was to compare blood pressure and endocrine responses in a cold pressure test in young healthy subjects who had shown increased blood pressure during an acutely increased sodium intake. Subjects (n = 53) added 121 mmol sodium into their normal diet for one week. If the mean arterial pressure had increased by a minimum of 5 mmHg compared to the control measure, they were selected for the experiments. The selected subjects (n = 8) were given 121 mmol supplemental sodium d-1 for 14 days after which they immersed the right hand into a cold (+10 degrees C) water bath for 5 min. The blood pressure increased (P < 0.05) during the test and was independent of the sodium intake. The plasma noradrenaline increased from 2.41 +/- 0.38 nmol l-1 to 2.82 +/- 0.42 nmol l-1 (P < 0.05) with normal diet and from 1.85 +/- 0.29 nmol l-1 to 2.40 +/- 0.37 nmol l-1 (P < 0.05) with high sodium diet. The starting concentrations and the endpoint concentrations were statistically similar. The plasma levels of natriuretic peptides (NT-proANP, ANP and BNP) did not change during the test, and the concentrations were independent of the sodium diet. To conclude, acutely increased sodium intake does not change blood pressure or hormonal responses in a cold pressor test in young healthy subjects.     

Differential effects of lower body negative pressure on forearm and calf blood flow

Modest degrees of lower body negative pressure (less than 20 mmHg) cause a reflex constriction of forearm resistance vessels attributable to a decrease in activity of cardiopulmonary mechanoreceptors. In the present study, we sought to determine whether the calf vessels respond similarly. Left forearm and right calf blood flows were measured simultaneously by strain-gauge plethysmography in 10 healthy volunteers. Forearm flows decreased significantly from control during negative pressures of 10, 15, or 20 mmHg, whereas calf flows did not decrease significantly until 20 mmHg; at 10, 15, and 20 mmHg, decreases in forearm flow were significantly greater than those of the calf. Similar results were obtained in a second series of experiments in which venous pooling in the right leg during lower body negative pressure was prevented by enclosing it in a boot. At 40 mmHg, or after a Valsalva maneuver, both forearm and calf vessels constricted markedly and to the same degree. It appears that the reflex reduction in blood flow to the skeletal muscles of the limbs resulting from deactivation of the low-pressure intrathoracic mechanoreceptors is directed primarily to the arm.     

Activation of VPAC1 receptors aggravates early atherosclerosis in hypercholesterolemic apolipoprotein E-deficient mice

Objective: Vasoactive intestinal peptide (VIP) is a 28-amino acid peptide widely expressed in the body and binding three types of receptors: VPAC₁-R, VPAC₂-R and PAC₁-R. Based on beneficial effects of VIP and VPAC₁-R agonists in mouse models of several chronic inflammatory disorders, we hypothesized that activation of VIP receptors would prevent atherosclerosis development in apolipoprotein E-deficient mice.Methods and results: Contrary to our hypothesis, administration of a VPAC₁-R agonist, (Ala^11,22,28)-VIP aggravated atherosclerotic lesion development in the aortic root of these mice compared to control mice. This was accompanied by a significant increase in the expression of MHC class II protein I-A^b, and suggests enhanced inflammatory activity in the vessel wall. The amount of macrophage-specific CD68 staining as well as serum cholesterol and triglyceride levels did not change as a result of the (Ala^11,22,28)-VIP treatment, i.e. the treatment resulted in significant changes in lipid accumulation in the lesions without changing the number of macrophages or systemic lipid levels. Interestingly, administration of VIP did not alter the course of the disease.Conclusion: Despite beneficial effects in murine models of several inflammatory disorders, VPAC₁-R activation aggravates atherosclerotic lesion formation in apolipoprotein E-deficient mice through enhanced inflammatory activity in the vessel wall.     

Interactions between sodium and calcium intake and blood pressure responses to norepinephrine and parathyroid hormone

The present study has examined the vascular responses to infusion of norepinephrine (NE) and parathyroid hormone (PTH 1-34) in animals subjected for a six month period to one of four dietary regimens. Some animals received normal calcium chow (1.0% Ca by weight) and drank water (subgroup A), others consumed the same chow, but water was replaced by 0.5% saline (subgroup B), a third group consumed chow which had 2.0% Ca content and also drank 0.5% saline (subgroup C) and a fourth group consumed the 2.0% Ca chow, but drank water (subgroup D). No differences were found in the pressor response to NE across subgroup A, B, and C, while pressor response to NE in subgroup D was markedly reduced. Depressor responses to PTH were not significantly different across any of the four groups. The ability of changes in calcium homeostasis to affect blood pressure responses to NE and PTH were evaluated in animals consuming reduced dietary calcium (0.1%) for two and four weeks and compared with animals on normal calcium intake (1.0%). This dietary treatment resulted in only mild effects on calcium balance; after four weeks no significant difference in plasma total calcium concentration was observed, but plasma PTH levels were increased in animals on the low Ca diet. No effects on the blood pressure response to NE or PTH infusion were observed after 2 weeks of dietary treatment. At four weeks, NE responses remained unchanged, while responses to PTH were blunted in animals on 0.1% Ca chow.(ABSTRACT TRUNCATED AT 250 WORDS)     

High dietary salt intake increases carotid blood pressure and wave reflection in normotensive healthy young men

Dietary salt intake is associated with high brachial blood pressure (BP) and increased risk of cardiovascular disease. We investigated whether changes in dietary salt intake are associated with changes in central BP and wave reflection in healthy volunteers. Ten healthy normotensive male volunteers (22-40 yr) participated in a 6-wk double-blind randomized crossover study to compare a low-dietary salt intake (60-80 mmol sodium/day) with a high-salt intake (low salt intake supplemented with 128 mmol sodium/day) on central BP and wave reflection. Brachial and carotid BP, carotid blood flow velocity, forward (P(f)) and backward (P(b)) pressure, wave intensity, body weight, and urinary electrolyte excretion were measured at the end of each crossover period. High salt intake significantly increased carotid systolic BP [98 (SD 11) vs. 91 mmHg (SD 13), P < 0.01] and increased wave reflection [ratio of backward to forward pressure (P(b)/P(f)) 0.13 (SD 0.02) vs. 0.11 (SD 0.03), P = 0.04] despite only small effects on brachial BP [114 (SD 9) vs. 112 mmHg (SD 6), P = 0.1]. Urinary sodium excretion and body weight were also increased following high salt intake. High salt intake disproportionately increases central BP compared with brachial BP as a result of enhanced wave reflection. These effects may contribute to the adverse effect of high dietary salt intake on the risk of cardiovascular disease.     

Differential effects of lower body negative pressure and upright tilt on splanchnic blood volume

Upright posture and lower body negative pressure (LBNP) both induce reductions in central blood volume. However, regional circulatory responses to postural changes and LBNP may differ. Therefore, we studied regional blood flow and blood volume changes in 10 healthy subjects undergoing graded lower-body negative pressure (-10 to -50 mmHg) and 8 subjects undergoing incremental head-up tilt (HUT; 20 degrees , 40 degrees , and 70 degrees ) on separate days. We continuously measured blood pressure (BP), heart rate, and regional blood volumes and blood flows in the thoracic, splanchnic, pelvic, and leg segments by impedance plethysmography and calculated regional arterial resistances. Neither LBNP nor HUT altered systolic BP, whereas pulse pressure decreased significantly. Blood flow decreased in all segments, whereas peripheral resistances uniformly and significantly increased with both HUT and LBNP. Thoracic volume decreased while pelvic and leg volumes increased with HUT and LBNP. However, splanchnic volume changes were directionally opposite with stepwise decreases in splanchnic volume with LBNP and stepwise increases in splanchnic volume during HUT. Splanchnic emptying in LBNP models regional vascular changes during hemorrhage. Splanchnic filling may limit the ability of the splanchnic bed to respond to thoracic hypovolemia during upright posture.     

Combination of dietary phytosterols plus niacin or fenofibrate: effects on lipid profile and atherosclerosis in apo E-KO mice

Patients with mixed dyslipidemias (increased LDL cholesterol and triglyceride as well as low HDL cholesterol levels) benefit from a combination of lipid-modifying drugs such as statins, niacin, fibrates and ezetemibe. However, safety, tolerability and cost are a concern in drug combination therapy. Dietary phytosterols reduce LDL cholesterol, and niacin or fenofibrate primarily reduces triglyceride and increases HDL-cholesterol levels. Thus, we hypothesized that a combination of phytosterols with niacin or fenofibrate will synergistically impact lipoprotein profile and atherogenesis in apo E-KO mice. Phytosterols alone significantly reduced plasma total cholesterol levels (14.1 vs. 16.9 mmol/L, P < .05) and the extent of atherosclerosis (0.42 vs. 0.15 mm(2), P < .05). The addition of fenofibrate to phytosterols increased plasma total cholesterol levels by >50% (14.1 vs. 21.6 mmol/L, P < .05) and decreased HDL-cholesterol concentrations by 50% (0.8 vs. 0.4 mmol/L). These changes were accompanied by slight reductions in the extent of atherosclerosis (0.42 vs. 0.34 mm(2), P > 0.05) as compared to controls, suggesting other potential anti-atherogenic effects of fenofibrate. Unlike fenofibrate, niacin caused an increase of 150% (P < .05) in HDL-cholesterol concentrations and a decrease of 22% (P < .05) in total cholesterol levels which were associated with significant reductions (65%, P < .05) in atherosclerotic lesion size as compared to controls. Neither the addition of niacin nor of fenofibrate reduced plasma triglyceride levels. In conclusion, the addition of niacin to phytosterols synergistically increases HDL-cholesterol levels, while a combination of phytosterols and fenofibrate results in no synergistic effects in apo E-KO mice. Further studies in other animal models are needed to establish synergetic effects between these lipid-modifying dietary and pharmacological agents.     

Blood pressure in relation to dietary calcium intake, alcohol consumption, blood lead, and blood cadmium in female nonsmokers

The interrelationship of dietary calcium (Ca) intake, alcohol consumption, blood lead (BPb), blood cadmium (BCd), age, and body mass index (BMI) to blood pressure was examined in 267 peasant women 40-85 years of age. They were residents of two rural areas in Croatia and differed with regard to dietary Ca intake: 100 women with low Ca intake (approximately 450 mg/day) and 167 women with relatively high Ca intake (approximately 940 mg/day). All of the women were nonsmokers and consumed very little or no alcohol. Median and range BPb values were 74 (29-251) microg/L in women with low Ca intake and 59 (21-263) microg/L in women with high Ca intake (p < 0.0002), whereas corresponding BCd values were 0.6 (0.2-3.6) microg/L and 0.6 (0.3-4.5) microg/L (p > 0.10). Results of multiple regression showed a significant (p < 0.05) increase in systolic blood pressure with age, BMI, and BCd, and marginally with alcohol consumption (multiple r = 0.48, p < 10(- 6)). An increase in diastolic blood pressure was significantly (p < 0.05) associated with BMI, age, and residence area (i.e., it was higher in women with low Ca intake), and marginally with BCd, and alcohol consumption (multiple r = 0.38, p < 10(-6)) When the two groups of women with different Ca intake were subdivided into consumers and nonconsumers of alcohol, BPb was related positively to alcohol consumption and inversely to Ca intake. The highest BPb was found in the subgroup of alcohol consumers with low Ca intake, and the lowest BPb in the subgroup of nonconsumers with high Ca intake: 78 (42-251) microg/L and 51 (22-192) microg/L, respectively (p < 10(-8)). Diastolic blood pressure was significantly higher in the former subgroup as compared to the latter: 95 (72-130) mm Hg and 90 (60-120) mm Hg, respectively (p < 0.05). This cannot be explained by age, BMI, or BCd, which were comparable in the two subgroups. The results indicate that alcohol consumption and low Ca intake can increase BPb, which may significantly contribute to an increase in diastolic blood pressure in female nonsmokers even at relatively low-level Pb exposure.