Urinary sodium excretion and blood pressure in chronic psychiatric in-patients.

Studies of populations or communities with no rise in blood pressure (BP) with advancing age and low prevalence of hypertension, may provide aetiological clues on the cause of hypertension. Within westernised societies, low blood pressures have been reported amongst chronic psychiatric in-patients and closed order secluded nuns. To investigate factors associated with BP in chronic psychiatric in-patients, we surveyed the BP and lifestyle factors in 89 such subjects in low security wards in three psychiatric hospitals. The average age of examines was 48.1 years (s.d. 15.8) and the patients had been in hospital for a mean of 8.6 years (range 1.1 to 51.7 years). The mean systolic and diastolic blood pressures of this group were 122.0 mm Hg (s.d. 14.2) and 76.9 mm Hg (s.d. 8.5) respectively. This was lower than pressures obtained when they were admitted to hospital (mean systolic BP change -17.1 mm Hg (s.d. 14), paired t-test P < 0.001; mean diastolic BP change -3.7 mm Hg (s.d. 12.2), paired t-test P < 0.001). BP at examination was significantly correlated with the urinary sodium to creatinine ratio (r = 0.302, P = 0.027), but not with the urinary sodium or potassium concentrations or potassium/creatinine ratio. The change in mean systolic BP (that is, the difference in BP between admission and examination) was significantly correlated with sodium/creatinine ratio (r = 0.62, P < 0.0001), urinary sodium concentration (r = 0.27, P = 0.045) and urinary sodium/potassium ratio (r = 0.36, P = 0.008). No relationship was found between BP and the nature of the psychiatric diagnosis or the type of psychotropic medication that was being prescribed. Stepwise multiple regression demonstrated that urinary sodium creatinine ratio and age were predictive of the change in systolic BP since admission to hospital. Our study confirms previous observations of lower mean systolic and diastolic blood pressures in chronic psychiatric subjects after a long in-patient stay. This fall is related to a low urine sodium excretion and suggests that a low dietary sodium intake may, in part, account for the low BP, or the difference between BP in the stressed and relaxed state, seen in these patients.     

Urinary potassium excretion and sodium sensitivity in blacks

Based on racial differences in urinary potassium excretion and responses to diuretics, we present a model suggesting that a major cause of sodium sensitivity in blacks is an augmented activity of the Na-K-2Cl cotransport in the thick ascending limb of Henle's loop. This would result in an increased ability to conserve not only sodium but also water, and an upward and rightward shift in the operating point of tubuloglomerular feedback, which may cause an increase in the glomerular capillary hydraulic pressure and predilection to glomerular injury with and without hypertension. In this sense, the biological implication of sodium sensitivity in blacks and in humans in general has ramifications above and beyond salt-evoked increase in blood pressure.     

Effects of nicotinic acid on insulin sensitivity and blood pressure in healthy subjects

Insulin resistance and hyperinsulinaemia are associated with hypertension although a causative relationship has not been established. The aim of this study was to determine whether a short term reduction in insulin sensitivity induced by nicotinic acid treatment (NA) would alter blood pressure. The study was a double-blind randomised placebo-controlled cross-over study. Seven healthy volunteers, three males and four females were randomised to placebo or NA 500 mg daily for 7 days then 1 g daily for a further 7 days. Hyperinsulinaemic euglycaemic clamp, indirect calorimetry, 24-h ambulatory blood pressure monitoring (ABPM) and forearm blood flow measurement (FABF) were performed at day 14 of each treatment phase. NA significantly reduced the glucose infusion rate required to maintain euglycaemia in all subjects (placebo vs NA; 31.5+/-4.2 vs. 26.2+/-4.6 micromol/kg/min, P = 0.002) associated with a decrease in non-oxidative glucose disposal. NA did not significantly alter 24-h mean systolic or diastolic blood pressure. Fasting glucose, insulin and non-esterified free fatty acid (NEFA) levels remained unchanged, energy expenditure and substrate oxidation were not altered by NA. These results suggest a short term reduction in insulin sensitivity with NA is not accompanied by a change in blood pressure. This may relate to the short duration of treatment, to a dissociation between insulin resistance and hypertension or to other homeostatic mechanisms which prevent blood pressure rising in subjects not predisposed to hypertension.     

Relationship of urinary kallikrein excretion to renal water and sodium excretion

The circadian rhythms of urine volume and urinary excretion of sodium, potassium, kallikrein, and aldosterone were analyzed by a multivariate method (cosinor method) in 20 healthy Japanese women on an ordinary diet. The relationship of urinary kallikrein and aldosterone excretion to urine volume and urinary sodium and potassium excretion was studied by assessing the correlation of the circadian rhythms. The acrophases in the circadian rhythms of urine volume (16:51) and urinary sodium excretion (16:55) appeared after the acrophase of urinary kallikrein excretion (15:28). There was a highly significant correlation between the circadian rhythm of urinary kallikrein excretion and the circadian rhythms of urine volume (r = 0.948) and urinary sodium excretion (r = 0.921). These results suggest that the renal kallikrein-kinin system participates in the regulation of renal water and sodium excretion in persons on an ordinary diet. A highly significant relationship between the acrophases in the circadian rhythms of urine volume and sodium excretion (r = 0.935) also suggests that water and sodium excretion may have a mutual influence on the kidneys. There were positive correlations between the circadian rhythms of potassium excretion and kallikrein excretion and potassium excretion and sodium excretion; and the latter relationship was relatively closer than the former. The acrophase in the circadian rhythm of aldosterone excretion did not correlate well with the acrophases of the other urine variables including sodium excretion.     

Urinary sodium excretion and its association with blood pressure in Nigeria: A nationwide population survey

Assessment of level of salt intake in a population is the first step toward planning strategies aimed at salt reduction. As a surrogate of salt intake, we measured a single 24‐hour urine sodium (uNa) of free‐living 2503 adults in a nationally representative sample of Nigerians drawn from 12 rural and urban communities; and evaluated the community‐level association of uNa with blood pressure (BP). Overall, the median (interquartile range (IQR)) of uNa was 99 (105) mmol, ranging from 23.8 (32.4) in rural north‐central to 172.8 (131.0) mmol in urban northwestern region. Daily uNa was significantly higher (p < .001) in men compared to women (107.1 vs 93.9 mmol); and urban compared to rural dwellers (114.9 vs 86.0mmol). About one‐half of participants excreted uNa in excess of recommended daily maximum value (86mmol). In a model adjusted for age, sex, body mass index (BMI), level of education, place of residence, and use of antihypertensive medication; being a man (odds ratio, OR 1.69, 95% confidence Interval CI, 1.21‐2.37, p = .002) and being < 60 years of age (OR 1.74, 95% CI 1.23‐2.45, p = .002), were associated with excreting higher than recommended uNa. In a fully adjusted model of the community‐level analysis, urinary sodium, potassium, and sodium‐to‐potassium ratio each showed no significant independent association with both systolic and diastolic BPs. Among adult Nigerians, the median daily uNa excretion was 99 mmol and it had no significant association with blood pressure indices.     

Effects of insulin on kidney function and sodium excretion in healthy subjects

Summary Insulin action on kidney function was evaluated in 8 healthy subjects, (mean age 27 years) using the euglycaemic clamp technique. Insulin was infused at rates of 0, 20 and 40 mU·min^–1·m^–2 over consecutive periods of 120 min resulting in plasma insulin concentrations of 8±2, 29±7 and 66±14 mU/l. The renal clearance of ⁵¹Cr-EDTA, lithium, sodium and potassium was determined during the last 90 min of each period. Sodium clearance declined with increasing plasma insulin concentrations (1.3±0.4, 1.0±0.3 and 0.5±0.2 ml·min^–1·1.73 m^–2, p<0.001), while glomerular filtration rate (108±21, 104±21 and 108±20ml·min^–1·1.73 m^–2) and lithium clearance (a marker of fluid flow rate from the proximal tubules) 29±5, 29±4 and 30±4 ml·min^–1·1.73 m^–2) remained unchanged. Calculated proximal tubular reabsorption of sodium and water was unchanged, while calculated distal fractional sodium reabsorption increased (95.5±1.5, 96.4±1.2 and 98.1±0.7%, p<0.001). Potassium clearance and plasma potassium concentration declined, whereas plasma aldosterone and plasma renin concentrations were unchanged. In conclusion, elevation of plasma insulin concentration within the physiological range has a marked antinatriuretic action. This effect is located distally to the proximal renal tubules.     

The effect of dietary sodium loading on the kinetics of sodium excretion and blood pressure regulation in essential hypertensive men

The kinetics of urinary sodium excretion defined as the rate of urinary sodium excretion during five-days oral sodium loading was investigated in 12 male patients with essential hypertension. The change in blood pressure under oral 200 mmol/24 h NaCl intake correlated inversely with the rate of urinary sodium excretion (r = -0.60, p less than 0.05), but did not significantly depend on the change in the absolute amount of excreted sodium. The rate of sodium excretion correlated directly with preload glomerular filtration rate (GFR) (r = 0.63, p less than 0.05), effective renal plasma flow (ERPF) (r = 0.78, p less than 0.01) and inversely with renal vascular resistance (RVR) (r = 0.67, p less than 0.01). The fall of renal plasma flow at moderate increment in the filtration fraction under sodium loading correlated directly with the rate of urinary sodium excretion (r = 0.73, p less than 0.01). The results suggest that: 1) the rate of sodium excretion is a more important factor in blood pressure regulation than the ability of the kidney to excrete the entire sodium load; 2) renal haemodynamics plays an indirect role in blood pressure regulation.     

Nighttime blood pressure and nocturnal dipping are associated with daytime urinary sodium excretion in African subjects

Blood pressure (BP) follows a circadian rhythm, with 10% to 15% lower values during nighttime than during daytime. The absence of a nocturnal BP decrease (dipping) is associated with target organ damage, but the determinants of dipping are poorly understood. We assessed whether the nighttime BP and the dipping are associated with the circadian pattern of sodium excretion. Ambulatory BP and daytime and nighttime urinary electrolyte excretion were measured simultaneously in 325 individuals of African descent from 73 families. When divided into sex-specific tertiles of day:night ratios of urinary sodium excretion rate, subjects in tertile 1 (with the lowest ratio) were 6.5 years older and had a 9.8-mm Hg higher nighttime systolic BP (SBP) and a 23% lower SBP dipping (expressed in percentage of day value) compared with subjects in tertile 3 (P for trend <0.01). After adjustment for age, the SBP difference across tertiles decreased to 5.4 mm Hg (P=0.002), and the SBP dipping difference decreased to 17% (P=0.05). A similar trend across tertiles was found with diastolic BP. In multivariate analyses, daytime urinary sodium and potassium concentrations were independently associated with nighttime SBP and SBP dipping (P<0.05 for each). These data, based on a large number of subjects, suggest that the capacity to excrete sodium during daytime is a significant determinant of nocturnal BP and dipping. This observation may help us to understand the pathophysiology and clinical consequences of nighttime BP and to develop therapeutic strategies to normalize the dipping profile in hypertensive patients.     

长期补钾补钙对盐敏感儿童血压及其尿钠代谢的影响

为观察长期适量补充钾盐及钙盐对盐敏感儿童血压及其尿钠代谢的影响。对为期２年的补钾补钙随机双盲安慰剂对照试验的２６１名儿童进行了盐敏感性测定。结果显示：盐敏感性儿童，补钾补钙组２年期血压增长值较安慰剂组低４．３／４．８ｍｍＨｇ（Ｐ＜０．０５），前者血压增长幅度较后者低３．６／７．０个百分点（Ｐ＜０．０５）；而盐不敏感儿童，补充组与安慰剂组间血压变化无显著性差异。盐敏感性儿童经补钾补钙后，夜８小时尿钠排泄量明显增加（Ｐ＜０．０１），且后者与其血压增长幅度呈负相关（ｒ＝－０．３９，Ｐ＜０．０１）。提示，适量增加钾和钙的摄入，通过与钠离子的相互复合作用，促进尿钠排泄，可降低盐敏感儿童血压的增长幅度。     

Urinary acid excretion in aged subjects

Urinary excretion of titratable acid and ammonium was investigated in 50 healthy volunteers in individual decades in subjects aged 20 to 70 years. The examination was made under control conditions and after acute loading with ammonium chloride (0.1 g/kg body weight). Titratable acid excretion calculated per 100 ml of creatinine clearance (^UTA^V/C_cr · 100) under control conditions increased with age (r = 0.366, p < 0.01). Acute acid loading was associated with a further increase in^UTA^V/C_cr · 100 which was significant (0.05 to 0.01) in all the examined age groups with the exception of those aged 61–70 years. The changes in^UTA^V/C_cr 100 paralleled those in fractional phosphate excretion (FE_p) both under control conditions and after acid loading (r = 0.591, p < 0.001). Urinary ammonium excretion calculated per 100 ml C_cr (^UNH₄ ^V/C_cr · 100) under control conditions did not change significantly with age. The increase in^UNH₄ ^V/C_cr · 100 after acute acid loading (at the time of the lowest urinary pH) was clearly expressed in subjects aged 21–30 years (p < 0.01). In individuals older than 50 years the increase in^UNH₄ ^V/C_cr · 100 was not significant. Urinary pH under control conditions did not change with age. After acid loading, the average values of urinary pH decreased below 5.0 in all the examined age groups and there was no significant difference between the old and young subjects. The obtained results are in keeping with the assumption that urinary net acid excretion by the aged kidney is predominantly influenced by changes in urinary titratable excretion. The results are compatible with the assumption that the promptness of the aged kidney to respond to an acute acid load is depressed in older subjects. The creation of a high hydrogen-ion concentration gradient is not affected by aging.     

Urinary kallikrein excretion in insulin-dependent diabetes mellitus and its relationship to glycemic control

The renal kallikrein-kinin system is thought to be involved in vasoregulatory and epithelial ion-transporting processes. Renal kallikrein has not been studied in patients with diabetes mellitus, a disease in which abnormalities of renal hemodynamics and electrolyte handling occur. The urinary excretion of this kallikrein was measured in 20 type I diabetic patients and 10 normal subjects. On a 120-meq Na diet, daily kallikrein excretion, determined by both esterase activity and direct RIA, in 12 poorly controlled diabetic patients [hemoglobin A1c (HbA1c) = 14.2 +/- 0.5% (mean +/- SEM)] was significantly greater (P less than 0.05) than excretion in 8 diabetic patients in good to moderately good control (HbA1c = 9.4 +/- 0.5%) or in 10 normal subjects. In these groups, urinary esterase activities were 9.4 +/- 1.0, 6.1 +/- 1.4, and 6.7 +/- 0.5 esterase units/24 h, respectively. Corresponding excretion values of immunoreactive kallikrein were 171 +/- 14, 118 +/- 26, and 123 +/- 11 micrograms/24 h. Creatinine clearances were similar in the three groups. Urinary kallikrein was also measured in 8 diabetic and 8 normal subjects during 7 subsequent days of 10 meq Na intake. It increased less in diabetic patients than in normal subjects during Na depletion (P less than 0.02). The increase in urinary kallikrein in the diabetic patients was inversely related to their HbA1c levels (r = 0.88; P less than 0.01). The effect of glycemic control on urinary kallikrein excretion was determined in nine diabetic patients. Initial glycemic control was achieved using an artificial endocrine pancreas (Biostator) and was maintained by continuous sc insulin infusion with a portable pump. Before glycemic control, urinary kallikrein was 190 +/- 30 micrograms/24 h (by RIA). After 8-12 days of glycemic control, excretion fell to 144 +/- 23 micrograms/24 h (P less than 0.02). The abnormalities in kallikrein excretion in diabetic patients were not correlated with differences in water, electrolyte, protein, glucose, or aldosterone excretion in any of the studies. These results show that kallikrein excretion was increased in patients with poorly controlled insulin-dependent diabetes, and excretion rose less in diabetic subjects with low Na intake than in normal subjects. Strict glycemic control decreased urinary kallikrein excretion. These findings suggest that the renal kallikrein-kinin system is functioning abnormally in diabetes mellitus.     

Urinary excretion of activatable kallikrein in one-kidney pole-ligated hypertensive rats

Kallikrein activatable by trypsin was found in the urine of normal rats, corresponding to about 33% of the total kallikrein excretion. This fraction was inhibited by aprotinin and kallikrein antiserum. There was no spontaneous activation at 20 degrees C for 24 h or at 37 degrees C for 15 h which indicates that the amount detectable in the urine may represent the levels of activatable kallikrein in the renal tubule. Sephacryl S-200 chromatography of the urine disclosed the presence of two forms of kallikrein, active and activatable, with apparent molecular weights of 30 000 and 34 500 respectively. These findings allow us to assume that the activatable fraction would correspond to prokallikrein, as described by others. In hypertensive one-kidney pole-ligated rats, the total urinary kallikrein did not differ from that excreted by solely uninephrectomized rats, though the active kallikrein showed a significant drop (P less than 0.001). These results suggest that in hypertensive rats there is an alteration in the activation mechanisms of kallikrein.     

Microvascular function relates to insulin sensitivity and blood pressure in normal subjects

BACKGROUND: A strong but presently unexplained inverse association between blood pressure and insulin sensitivity has been reported. Microvascular vasodilator capacity may be a common antecedent linking insulin sensitivity to blood pressure. To test this hypothesis, we studied 18 normotensive and glucose-tolerant subjects showing a wide range in insulin sensitivity as assessed with the hyperinsulinemic, euglycemic clamp technique. METHODS AND RESULTS: Blood pressure was measured by 24-hour ambulatory blood pressure monitoring. Videomicroscopy was used to measure skin capillary density and capillary recruitment after arterial occlusion. Skin blood flow responses after iontophoresis of acetylcholine and sodium nitroprusside were evaluated by laser Doppler flowmetry. Insulin sensitivity correlated with 24-hour systolic blood pressure (24-hour SBP; r=-0.50, P<0.05). Capillary recruitment and acetylcholine-mediated vasodilatation were strongly and positively related to insulin sensitivity (r=0.84, P<0.001; r=0.78, P<0.001, respectively), and capillary recruitment was inversely related to 24-hour SBP (r=-0.53, P<0.05). Waist-to-hip ratio showed strong associations with insulin sensitivity, blood pressure, and the measures of microvascular function but did not confound the associations between these variables. Subsequent regression analysis showed that the association between insulin sensitivity and blood pressure was not independent of the estimates of microvascular function, and part of the variation in both blood pressure (R2=38%) and insulin sensitivity (R2=71%) could be explained by microvascular function. CONCLUSIONS: Insulin sensitivity and blood pressure are associated well within the physiological range. Microvascular function strongly relates to both, consistent with a central role in linking these variables.