Urinary calcium excretion, sodium intake and blood pressure in a multi-ethnic population: results of the Wandsworth Heart and Stroke Study.

BACKGROUND: Hypertension is associated with increased urinary calcium excretion (UCa). A high sodium intake increases both UCa and blood pressure (BP). However, it is not clear whether these effects are modified by gender or ethnic origin. OBJECTIVES: To examine the relationships between BP, urinary sodium (UNa), gender and ethnic origin with both daily and fasting UCa in a population-based study. DESIGN AND METHODS: Out of 1577 individuals taking part in a cross-sectional survey, 743 were considered for the present analysis (407 women, 336 men) as they were all untreated, had provided a complete 24-h urine collection, and had all measurements of anthropometry, BP, UNa and UCa. They were 277 whites, 227 of black African origin and 239 South Asians. Comparisons were also carried out in the 690 participants who also provided 3-h fasting urine collections. RESULTS: After adjustment for confounders including age, and gender, 24-h UCa was significantly and independently associated with ethnic origin, BP and UNa. Mean 24-h UCa was 4.62 (s.e. 0.11) mmol/d in whites, 3.33 (0.12) in South Asians and 3.16 (0.13) in blacks (P < 0.001). a 100 mmol higher UNa predicted a 1.04 mmol higher daily UCa (P < 0.001), and a 20 mm Hg higher systolic BP predicted a 0.28 mmol higher UCa. The slopes were not significantly different by ethnic group. The ethnic differences in UCa were present when fasting UCa was used instead (1.64 [0.05] micromol/min in whites, 1.08 [0.06] in South Asians and 1.13 [0.06] in blacks; P < 0.001). CONCLUSIONS: These results indicate that BP, salt intake and ethnic origin are independent predictors of UCa in an unselected population. These relationships are unlikely to be the result of differences in Ca intake or intestinal Ca absorption as they are seen also after an overnight fast, suggesting that they may reflect differences in renal tubular handling. The estimated effects of either BP or sodium intake on UCa, sustained over many years, may be associated with significant effects on bone calcium content.

Epithelial sodium channel activity is not increased in hypertension in whites.

Abnormal renal sodium transport causing excess reabsorption of sodium may be one mechanism that causes high blood pressure. For example, increased activity of epithelial sodium channels in the distal tubule is the cause of high blood pressure in Liddle's syndrome, a rare familial form of hypertension. We have shown that the increase in sodium channel activity can be detected in the nose using transepithelial potential difference measurements in 1 family with Liddle's syndrome. We therefore used nasal potential difference measurements to look for increased sodium channel activity in white patients with essential hypertension. Transnasal potential difference was measured in 42 white hypertensive (HT) subjects and 38 white normotensive (NT) subjects before and after topical application of 10(-4) mol/L of amiloride. There was no difference in maximum potential between HT and NT subjects (HT, -18.8+/-0.9 mV; NT, -18.2+/-1.0 mV) (values mean+/-SEM; lumen-negative with respect to the submucosa). However, the postamiloride potential was significantly higher (HT, -12.6+/-0.7 mV; NT, -10.5+/-0.7 mV; P=0. 015) and the change in potential in response to amiloride significantly lower (HT, 6.2+/-0.5 mV, 33.1+/-2.0%; NT, 7.7+/-0.6 mV, 41.9+/-2.0%; P=0.046 and 0.003, respectively) in HT than in NT subjects. These results suggest that sodium channel activity is not increased in whites with essential hypertension and indicate that sodium channel overactivity similar to that seen in Liddle's syndrome is unlikely to be the cause of high blood pressure in this group. Increased postamiloride potential may reflect increased activity of chloride channels or amiloride-insensitive sodium channels.

Glucose load and renal sodium handling in mild essential hypertension on different sodium intakes.

The aims of the present study were to investigate the effects of changes in sodium intake in patients with untreated mild essential hypertension on the hormonal (plasma renin activity and aldosterone) and renal tubular responses to short-term hyperinsulinemia as achieved by an oral glucose tolerance test (OGTT). Fourteen patients with essential hypertension (mean age, 46 years; average blood pressure (BP), 151/96 mm Hg) were studied. After a 1 week run-in period on their usual diet they entered a randomized double-blind crossover study of a week of low (10 mmol/day) vs a week of high (350 mmol/day) sodium intake. On the last day of each diet they underwent a standard 2-h OGTT. Blood and urines were taken hourly and segmental tubular sodium handling was assessed by the endogenous lithium clearance. The results demonstrate that the plasma insulin and glucose response to a short-term oral glucose load were not influenced significantly by the changes in dietary sodium intake. However, the glucose load was associated with marked renal sodium retention in the absence of any change in systemic BP. The reduction in renal sodium excretion was independent of circulating aldosterone but appeared to be due to an increase in renal distal tubular re-absorption.

A molecular epidemiological case-control study of lung cancer.

Polycyclic aromatic hydrocarbon-DNA adducts were measured by ELISA in peripheral leukocytes from 119 non-small cell lung cancer patients and 98 controls at the Columbia-Presbyterian Medical Center. Thirty-one cases had adduct measurements in leukocytes, lung tumor, and nontumor specimens collected at surgery, and 34 had paired leukocyte and tumor specimens. Information on smoking, diet, and occupational exposure was collected. After adjustment for age, gender, ethnicity, season, and smoking, adducts in leukocytes were significantly higher in cases (P < 0.01) than controls; the odds ratio was 7.7 (95% confidence interval = 1.7-34; P < 0.01). Adducts in leukocytes were increased significantly in smokers and ex-smokers compared to nonsmokers among cases and controls (separately and combined) after adjusting for age, gender, ethnicity, and season (P < 0.05). The cases and controls differed in several respects: (a) adducts increased with the number of cigarettes smoked among the 51 cases who were current smokers (P = 0.05) but not among the current smokers in the controls; and (b) a seasonal variation in DNA binding, corresponding to that reported for aryl hydrocarbon hydroxylase inducibility, was observed in cases but not in controls. Among the cases, adducts in leukocytes were correlated more strongly with adducts in the lung tumor tissue than with those in nontumor lung tissue. The results in leukocytes are consistent with a constitutional susceptibility to lung cancer, which results in greater DNA damage from carcinogens in cigarette smoke. They suggested that it may ultimately be possible to use biomarkers such as adducts to identify individuals who would benefit most from early intervention.

Mechanism of carbachol-evoked contractions of guinea-pig ileal smooth muscle close to freezing point.

1. The effect of lowering the temperature to near freezing-point upon the contractions and [3H]-inositol phosphate responses to carbachol were investigated in longitudinal smooth muscle from the guinea-pig ileum. 2. The peak amplitude of the contraction to a single application of 100 microM carbachol was the same at 37 degrees C and temperatures near freezing-point. However, the sensitivity to carbachol was reduced upon lowering the temperature and the time to peak contraction was increased from 5-10 s to 2-10 min. Even when the temperature was maintained near freezing-point, washing off carbachol produced a relaxation and eventual return of tension to basal levels. 3. Incubating the tissue in 140 mM K+, calcium-free solution or in calcium channel antagonists significantly reduced the carbachol-induced contraction to 10-30% of the control at 37 degrees C and also at 3 degrees C. Thus the majority of the activator calcium required for contraction entered the tissue via voltage-dependent calcium channels (VDCs) at both 37 degrees C and 3 degrees C. 4. The contractions produced by high potassium solutions were less at temperatures close to freezing-point than those at 37 degrees C suggesting that voltage-dependent calcium entry was inhibited as the temperature was lowered. 5. A small part of the contractile response to 100 microM carbachol was resistant to the removal of extracellular calcium at both 37 degrees C and 3 degrees C and this component was increased under depolarizing conditions. This suggests that the release of stored calcium contributes to a minor degree to contraction at both 37 degrees C and 3 degrees C.6. Although 100 microM carbachol produced a statistically significant rise in several [3H]-inositol phosphate isomers at both 37 degrees C and 3 degrees C, the production of [3H]-inositol phosphates was less at 3 degrees C than at 37 degrees C and the increase in their production caused by carbachol was much slower.7. These results suggest that the carbachol-induced contraction at 3 degrees C utilizes both calcium entry through VDCs and calcium release from intracellular stores, as at 37 degrees C. The components of the responses dependent upon intracellular calcium release at 37 degrees C and at temperatures near freezing-point were similar. However, the production of [3H]-inositol phosphates, including the calcium-mobilizing second messenger inositol (1,4,5) trisphosphate (Ins(1,4,5)P3), is reduced at such low temperatures.