Age, blood pressure, renin and urinary electrolytes in primary hypertension and in the normotensive state

One hundred and twenty-three patients, sixty-four men and fifty-nine women, with primary hypertension were studied with regard to supine and sitting blood pressure (BP), plasma renin activity (PRA) during basal and stimulated conditions, and urinary sodium and potassium excretions. The patients ranged in age from 20 to 76 (mean 48) years. A control material of 120 normotensive subjects, forty-nine men and seventy-one women, with an age range 22--78 (mean 47) years were studied during the same strictly standardized conditions. The two populations were compared statistically. The mean basal PRA level, measured after 1 h supine rest, was significantly higher in the hypertensive subjects, while the upright PRA, determined after ambulation for 3--4 h, was the same in the two groups. On the contrary, the stimulated mean PRA, measured 3--4 h after intake of 80 mg frusemide orally was significantly lower in the hypertensive subjects. No relationships could be demonstrated between PRA and the 24 h urinary electrolyte excretions. An age dependent decrease of upright and stimulated PRA was demonstrated only in the hypertensive population. Applying our previously published reference ranges for stimulated PRA, 16% of the hypertensive patients were considered to have low renin hypertension.     

Relationships between blood pressure, age, plasma renin activity and electrolyte excretion in normotensive subjects

Plasma renin activity (PRA), supine and sitting blood pressure (BP) and urinary sodium and potassium excretion were studied in 120 normotensive subjects aged 22--78 years, during strictly standardized conditions. PRA was measured after 1 h supine rest (basal PRA) after ambulation for 3--4 h (upright PRA) and after stimulation with 80 mg frusemide orally (stimulated PRA). PRA was determined with a new, simple, accurate and sensitive radioimmunoassay method. Supine and sitting systolic BP increased with age but no such correlation was found for the diastolic BP. No correlation could be shown between the BP levels and either the sodium or the potassium excretions. PRA levels increased about two-fold from basal to upright levels and about four-fold from basal levels after stimulation. No differences in mean PRA-levels were seen between males and females. We could not demonstrate any correlations between PRA-levels and 24 h sodium or potassium excretions, nor was there any relationship between age and PRA. Reference ranges are given for basal, upright and stimulated PRA in normotensive subjects. From these reference values a rational and clinically useful subdivision into low, normal and high renin groups can be made for hypertensive patients.     

The renin-aldosterone system in exaggerated natriuresis of essential hypertension

1. The effect of intravenous loading with 500 ml of sodium chloride solution (50 g/l) on plasma renin concentration, plasma aldosterone concentration, urinary sodium excretion and mean blood pressure was studied in 15 young patients with mild essential hypertension and 10 healthy normotensive control subjects. 2. Plasma renin concentration and plasma aldosterone concentration were suppressed to the same degree during loading in both the hypertensive and normotensive groups. Urinary sodium excretion was significantly higher in the hypertensive patients than in the normotensive subjects. Mean blood pressure increased slightly in both groups. 3. Plasma renin concentration and plasma aldosterone concentration were significantly correlated in both groups before sodium loading. The increase in urinary sodium excretion was significantly correlated to the suppression of plasma aldosterone concentration in the hypertensive, but not in the normotensive, group. No correlation was found between changes in urinary sodium excretion and changes in plasma renin concentration or mean blood pressure. 4. The results indicate that the suppressibility of the renin-aldosterone system by hyperosmotic sodium chloride solution is normal in young patients with mild essential hypertension. It is suggested that the changes in plasma aldosterone concentration induced by sodium loading might be involved in the regulation of exaggerated natriuresis in essential hypertension.     

Temporal enhancement of renin-aldosterone blockade by enalapril, an angiotensin-converting enzyme inhibitor

Interruption of the renin-aldosterone system with angiotensin-converting enzyme inhibitors (CEI) should result in a low aldosterone secretion, but most investigators have measured aldosterone production only indirectly by plasma aldosterone (PA) levels or urinary metabolites. We evaluated the effects of CEI of the aldosterone secretion rate (ASR) and compared them with PA, urinary tetrahydroaldosterone (THA), plasma renin activity (PRA), and electrolyte balance in six normotensive subjects in a metabolic unit during a control period (5 days) and during administration of 10 mg/day enalapril for 28 days. Our results demonstrated that (1) the ASR did not decline until after 1 wk of CEI therapy and this was reflected by a corresponding decline in the urine potassium:sodium ratio, (2) upright PA levels at day 1 declined, but supine PA levels were unchanged, (3) THA excretion remained essentially unchanged and the THA:ASR ratio rose progressively during therapy, (4) PRA rose and was maximal on day 3, but subsequently declined. In conclusion, enalapril-induced hypoaldosteronism required several days to become demonstrable and this was not accurately assessed by PA or THA--possibly due, in part, to altered aldosterone metabolism. The simultaneous decline in both PRA and ASR could be due to a decrease in renin substrate. Caution is therefore warranted when assessing aldosterone secretion indirectly by either PA levels or urinary metabolites during CEI therapy.     

Abnormally sustained aldosterone secretion during salt loading in patients with various forms of benign hypertension; relation to plasma renin activity

Among 25 patients with benign, essential hypertension, and an equal number with other benign forms of hypertension, without serious cardiac, renal, or cerebrovascular impairment, 41 cases failed to reduce aldosterone excretion rates into the normal range (less than 5 mug/day) on a daily intake of 300 mEq of sodium. The hypertensive patients excreted slightly less than the normal fraction of labeled aldosterone as acid-hydrolyzable conjugate. Secretion rates were significantly higher in the hypertensive patients than in normotensive controls taking the high-sodium intake.On a 10 mEq sodium intake, the increase in excretion and secretion rates of aldosterone in the hypertensive patients could be correlated with plasma renin activity (PRA). The patients with the least increase in PRA had subnormal increase in aldosterone secretion and excretion, while unusually large rises in aldosterone secretion accompanied high PRA, especially in the cases with increased plasma angiotensinogen induced by oral contraceptives.The persistence of inappropriately high aldosterone secretion in most hypertensive patients during sodium loading could be related to a higher PRA than that found in normotensive controls under comparable conditions. In other hypertensives, whose PRA was unresponsive to sodium depletion, there was no significant correlation between PRA and aldosterone output, and no known stimulus to aldosterone production was detected. Five obvious cases of hyperaldosteronism were found among the 16 low-renin patients. The cause of the nonsuppressible aldosterone production in the other low-renin cases remains to be determined.     

Effect of furosemide on urinary kallikrein excretion in patients with essential hypertension

The effect of furosemide on urinary kallikrein excretion was studied in 10 patients with essential hypertension and 9 normal volunteer subjects. After intravenous administration of furosemide and 2 hours of upright posture, urine volume (UV), urinary sodium (UNaV) and potassium (UKV) excretion, plasma renin activity (PRA), plasma aldosterone concentration (PAC) and urinary kallikrein markedly increased. However, the augmentation of urinary kallikrein in patients with essential hypertension (1.50 +/- 0.19 EU/2 hr) was less remarkable than that in normal subjects (2.33 +/- 0.24 EU/2 hr), although the same degrees of response were observed in PRA and PAC. The increments of UV, UNaV and UKV in patients with essential hypertension were also significantly lower than in normal subjects. Significant positive relations were found between urinary kallikrein and UV or UNaV in both hypertensive and normotensive groups, but there was no such correlation before fursemide administration. It is likely that diuresis and natriuresis induced by furosemide are somehow associated with an increase in urinary kallikrein excretion. Blunted response of urinary kallikrein in essential hypertension may suggest an abnormality in the renal kallikrein-kinin system in this disease.     

Studies of the control of plasma aldosterone concentration in normal man: I. Response to posture, acute and chronic volume depletion, and sodium loading

The peripheral plasma levels of aldosterone, renin activity (PRA), potassium, corticosterone, cortisol, and in some cases angiotensin II, were measured in normal subjects undergoing postural changes, acute diuretic-induced volume depletion, and alterations in dietary sodium. On a 10 mEq sodium/100 mEq potassium intake, subjects supine for 3 consecutive days had identical diurnal patterns of PRA, angiotensin II, aldosterone, cortisol, and corticosterone, with peaks at 8 a.m. and nadirs at 11 p.m. With an increase in sodium intake to 200 mEq, plasma levels of aldosterone and PRA fell to one-third their previous levels but the diurnal pattern in supine subjects was unchanged and again parallel to that of cortisol and corticosterone. There was no diurnal variation of plasma potassium on either sodium intake in the supine subjects. On a 10 mEq sodium/100 mEq potassium intake, supine 8 a.m. plasma aldosterone (55+/-7 ng/100 ml) and PRA (886+/-121 ng/100 ml per 3 hr) increased by 150-200% after subjects were upright for 3 hr. However, even though the patients maintained an upright activity pattern, there was a significant fall in plasma aldosterone to 33+/-5 ng/100 ml at 11 p.m. Potassium levels varied in a fashion parallel to aldosterone and PRA. Plasma cortisol and corticosterone had a diurnal pattern similar to that found in supine subjects. In response to acute diuretic-induced volume depletion, the nocturnal fall in aldosterone levels did not occur. The 11 p.m. value (102+/-20 ng/100 ml) and the 8 a.m. value postdiuresis (86+/-15 ng/100 ml) were both significantly greater than the prediuresis levels. PRA showed a similar altered pattern while potassium levels fell throughout the day. In some but not all studies, changes in plasma aldosterone coincided with changes in plasma cortisol, corticosterone, and/or potassium. However, in all studies, changes in plasma aldosterone were invariably associated with parallel changes in plasma renin activity and/or angiotensin II levels. These findings support the concept that PRA is the dominant factor in the control of aldosterone when volume and/or dietary sodium is altered in normal man.     

Intra-erythrocyte sodium and (Na+,K+-activated)-ATPase concentration and urinary aldosterone excretion in spontaneously hypertensive rats

1. Intra-erythrocyte sodium, potassium, ATP and (Na+,K+-activated)-ATPase concentrations and urinary aldosterone excretion were compared in 3-month-old spontaneously hypertensive rats (n = 11) and normotensive Wistar-Kyoto control rats (n = 11). 2. Spontaneously hypertensive rats exhibited significantly higher intra-erythrocyte sodium concentration (5.5 +/- 1.3 vs 4.0 +/- 1.1 mmol/l of erythrocytes, P less than 0.01). No significant difference was found in intra-erythrocyte potassium. ATP or (Na+,K+-activated)-ATPase concentration. 3. Mean urinary aldosterone excretion was significantly lower in spontaneously hypertensive rats (66.3 +/- 6.5 pmol/24 h) than in Wistar-Kyoto rats (90.5 +/- 10.6 pmol/24 h, P less than 0.01). No significant relationship between urinary aldosterone and intra-erythrocyte sodium concentration was found in spontaneously hypertensive or Wistar-Kyoto rats or in the pooled group. 4. These results are thus consistent with previous findings of an increased intracellular sodium concentration in spontaneously hypertensive rats, but do not support the hypothesis that aldosterone is a dominant regulator of intracellular sodium concentration.     

Sequential responses of the renin-angiotensin-aldosterone axis to acute postural change: effect of dietary sodium.

The simultaneous levels of plasma renin activity (PRA), angiotensin II (A II), and aldosterone (PA) were frequently assessed in 13 normal subjects following acute postural change (assumption of upright posture or returning to the supine position) on low (10 mEq.) and high (200 mEq.) sodium (Na+) intakes. The rate of response of aldosterone secretion was also correlated with changes in the metabolic clearance rate (MCR) of aldosterone. Significant increments of PRA and A II on either sodium intake occurred within 5 to 20 minutes; the peak values occurred within 90 minutes and tended to plateau until the end of the study (240 minutes). The mean absolute peak levels were approximately 2 to 3.5-fold greater than control. Increments of PA were initially delayed 20 to 30 minutes, but peak levels also were achieved by 90 minutes. The secretion rate of aldosterone increased 4-fold on the 10 mEq. Na+ and 2-fold on the 200 mEq. Na+ intake even though MCR declined 30 to 40 per cent in the upright posture. Sodium restriction enhanced the rate and magnitude of response of all parameters. Specifically, the slope of the regression relationship between PRA and PA was more than 4-fold steeper in the sodium-restricted than sodium-loaded subjects. From the rate of decline in PRA following resumption of supine posture, the half-life of PRA was estimated to be 14 to 15 minutes. The present study demonstrates that acute changes in posture are associated with closely correlated changes in PRA or A II. To varying degrees, it appeared that sympathetic activity, intravascular volume, diurnal secretion, and the sodium ion play a role in the sequential responses of these parameters to acute postural alterations.     

Deoxycorticosterone excretion in normal, hypertensive and hypokalaemic subjects.

1. Radioimmunoassay has been used to detect and estimate the urinary excretion of deoxycorticosterone (DOC) in normal, hypertensive and hypokalaemic subjects. The range of excretions in ten healthy normal subjects was 41-232 pmol (13.7-76.7 ng) daily, with a mean of 124 pmol (41 ng). 2. In fourteen subjects with essential hypertension without metabolic disturbance the range found was 29-144 pmol (9.7-47.7 ng) daily, with a mean of 87 pmol (28.8 ng), which is not significantly different from that in normal subjects. 3. In twelve patients with Cushing's syndrome due to adrenal cortical hyperplasia the range found was 26-542 pmol (8.7-179 ng). Ten of these twelve patients had values within normal limits. 4. Of nine subjects showing hypokalaemia, eight had elevated excretion of deoxycorticosterone with values from 263 to 5515 pmol (87-1820 ng) daily. Seven of these were hypertensive and two were normotensive. The elevated excretion of deoxycorticosterone found in hypokalaemic subjects is thus not confined to those with hypertension. 5. No correlation has been found between excretion rates for aldosterone and deoxycorticosterone. Raised excretion of the latter provides an indicator of disturbed adrenal cortical metabolism.     

Abnormal cation composition and transport in erythrocytes from hypertensive patients

Red cell sodium and potassium were determined in 100 untreated subjects with uncomplicated essential hypertension and compared with the values from 908 healthy normotensive control subjects. Red cell sodium concentration (expressed as mmol/l of erythrocytes) was significantly higher in hypertensive than in normotensive subjects. Red cell potassium concentration (in mmol/l of erythrocytes) was not significantly different in the two groups. Passive efflux of red cell potassium into buffered isotonic sucrose solution determined in eight hypertensive and nine normotensive subjects showed a lower potassium efflux rate in the hypertensive subjects. Comparison of active sodium efflux in sixteen hypertensive and fourteen normotensive subjects showed that ouabain-sensitive active sodium efflux was higher in red cells of normotensive than in those of hypertensive subjects.     

The renin-angiotensin-aldosterone system in decompensated cirrhosis: its activity in relation to sodium balance

Plasma renin activity (PRA), plasma renin concentration (PRC), plasma angiotensin II concentration (AII), plasma and urinary aldosterone (PA, UA) and urinary sodium excretion (UNaV) were measured in 51 normal controls, 16 patients with decompensated cirrhosis (i.e. ascites and/or oedema present) in sodium equilibrium (Group 1) and 13 patients with decompensated cirrhosis in a phase of active sodium retention (Group 2). In Group 1 the mean supine and erect values, although lower, were not significantly different from controls. In Group 2 the mean values were significantly elevated, but several individual values were within the normal range; there were significant direct relationships between plasma renin activity and plasma renin concentration (r = 0.85, p less than 0.001 erect), plasma renin concentration and plasma angiotensin II concentration (r = 0.86, p less than 0.001 erect), and plasma angiotensin II concentration and plasma aldosterone (r = 0.70, p less than 0.01 erect). In Group 2 there was an inverse correlation between urinary sodium excretion and both urinary aldosterone (r = -0.50) and erect plasma aldosterone (r = -0.36) but, perhaps because of the narrow range of sodium excretion rates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronism is not essential for the maintenance of established ascites, but do not exclude a role for aldosterone in the control of sodium excretion if it is accepted that renal tubular sensitivity to aldosterone is increased in these patients. In Group 2, the raised mean plasma and urinary aldosterone levels and the trend towards an inverse relationship with urinary sodium excretion suggests a role for aldosterone in the active retention of sodium. It appears that stimulation of the renin-angiotensin system is the major factor in the elevation of plasma aldosterone; there was no relationship between plasma aldosterone and either plasma sodium or potassium levels. The mechanism of renin hypersecretion is unclear but this may represent part of a sympathetically mediated response in order to maintain blood pressure. The close relationship between plasma renin activity and plasma renin concentration indicates that the former is a valid measure of circulating renin levels in cirrhosis, despite low renin-substrate levels.     

Normotension with decreased plasma renin activity and low serum ionic calcium levels: a prehypertensive state?

We studied the relationships between the renin-angiotensin-aldosterone system and calcium and magnesium levels in both serum and urine in 51 volunteer normotensive subjects, divided into two groups. Group 1 was made up of the 25 subjects whose levels of plasma renin activity were the lowest (1.93 +/- 0.70 ng/ml/hr). Group 2 comprised the 26 subjects with the highest plasma renin activity levels (4.80 +/- 0.84 ng/ml/hr). The following parameters were measured on all subjects: plasma renin activity and plasma and urinary aldosterone levels (by radioimmunoassay), serum ionic calcium levels (by Nova-2), total serum calcium, and serum and urinary magnesium values (by atomic absorption), serum and urinary sodium and potassium levels (by flame photometry), and creatinine clearance. In the group with low plasma renin activity (group 1), our findings included low serum ionic calcium levels (P less than .001); high coefficients of plasma aldosterone/plasma renin activity and urinary aldosterone/plasma renin activity (P less than .001); a significant correlation between the serum ionic calcium level and plasma renin activity (P less than .001); and an inverse correlation between systolic arterial tension and the serum ionic calcium level (P less than .05). These changes were more similar to change described in hypertensive patients with low plasma renin activity than to the findings in group 2 subjects. We speculate that normotensive subjects with low plasma renin activity present significant changes in the relationship between the renin-angiotensin-aldosterone system and sodium and calcium levels, and that this group is at risk for hypertension. A diet low in sodium and high in calcium could be an effective preventive measure.     

Renin-angiotensin-aldosterone system in exaggerated natriuresis of chronic glomerulonephritis

Angiotensin II (AII) and aldosterone (Aldo) in plasma, blood pressure (BP) and urinary excretion of sodium were studied before, during and in two periods after intravenous sodium loading with 500 ml of sodium chloride solution (50 g/l) in 11 normotensive and 10 hypertensive patients with histologically verified chronic glomerulonephritis and creatinine clearance in the range from 11 to 167 ml/min, and in 10 normotensive control subjects. The absolute increase of sodium excretion during loading was higher in the patients grouped together and in the hypertensives alone, but not in the normotensive patients when compared with the control subjects. No correlation was found between sodium excretion and control mean BP or change in mean BP during loading. AII and Aldo were suppressed during loading in both patients and control subjects. In the patients but not in the control subjects the increase of sodium excretion correlated positively with pre-infusion value of AII and negatively with change in AII during the sodium loading. No correlation was found between sodium excretion and Aldo and changes of Aldo. In conclusion, the results might suggest that the renin-angiotensin system is involved in the regulation of exaggerated natriuresis in chronic glomerulonephritis.     

A Specific Role for Saline or the Sodium Ion in the Regulation of Renin and Aldosterone Secretion

It is well established that in normal man the renin-angiotensin-aldosterone system is responsive to changes in volume. The present study was performed to determine whether sodium has an action apart from volume in the regulation of the secretion of renin and aldosterone. Acute volume expansion was induced either by saline, dextran, or glucose infusion in supine, normal subjects in balance on a 10 meq sodium/100 meq potassium diet. Plasma renin activity (PRA), angiotensin II (A II), aldosterone (PA), cortisol, serum sodium, and potassium were measured every 10 min for the first 30 min and then at 1, 2, 4, 6, and 8 h.During saline infusion (500 cm(3)/h for 6 h) mean PRA and A II levels declined very rapidly, falling significantly below control at 10 min (P < 0.01) and by 50% at 60 min. Thereafter, the rate of fall was more gradual, reaching a nadir at 360 min (70-80% below control). PA declined in a parallel pattern except that a significant fall did not occur until 30 min.In contrast to saline, dextran infusion (250 cm(3)/h for 4 h) did not produce a significant fall in PRA, A II, or PA until 4 h after the start of the infusion despite equivalent volume expansion. On the other hand, the infusion of 5% glucose and water (500 cm(3)/h for 6 h) did not produce a significant decline in PRA, A II, or PA over the first 6 h of the study. Although the response rate of PRA, A II, and PA was different in each of the three infusion studies, these parameters were significantly correlated within each study. Serum sodium and potassium levels did not change during any study except dextran infusion, where a significant fall in both occurred at 120 min. In all the infusion studies, plasma cortisol levels gradually declined during the 8-h study period consistent with its expected rhythm of diurnal secretion.These results demonstrate that rate of response of the renin-angiotensin-aldosterone system to acute volume expansion with saline differed from that with dextran and glucose infusion in sodium-depleted man. The data support a specific role for volume expansion with saline or the sodium ion per se in the regulation of renin and aldosterone.     

Plasma levels of atrial natriuretic peptide in patients with borderline and essential hypertension

Plasma levels of atrial natriuretic peptide (ANP) were measured in outpatients with borderline hypertension (n = 15) and essential hypertension (n = 13) and in normotensive subject (n = 11). There were no significant differences among the three groups in age, serum protein, albumin, or electrolyte levels, plasma renin activity (PRA), or plasma concentrations of aldosterone and cortisol. The plasma ANP levels in the normotensive, borderline hypertensive, and essential hypertensive subjects were 36 +/- 6 pg/ml (mean +/- S.E.), 64 +/- 11 pg/ml, and 82 +/- 14 pg/ml, respectively. The levels in the essential hypertensive subjects were significantly (p less than 0.05) higher than those in the normotensives. In both borderline and essential hypertensives (n = 28), the plasma ANP levels were significantly correlated positively with systolic blood pressure (r = +0.385, p less than 0.05), and negatively with PRA (r = -0.484, p less than 0.05) and serum total calcium (r = -0.516, p less than 0.01). These results suggest that the elevation of circulating ANP in hypertensives is involved in the pathogenesis of hypertension.     

Validity of the aldosterone-renin ratio used to screen for primary aldosteronism

OBJECTIVE: To determine whether the calculated ratio of plasma aldosterone concentration (PAC) to plasma renin activity (PRA), a proposed screening test for primary aldosteronism, provides a renin-independent measure of circulating aldosterone that is suitable to judge whether PAC is inappropriately elevated relative to PRA. SUBJECTS AND METHODS: This study consisting of 221 black and 276 white subjects with previously diagnosed essential hypertension was conducted between 1996 and 2000. Antihypertensive drugs were withdrawn for at least 4 weeks; PAC and PRA were measured while subjects were supine and then seated after 30 minutes of ambulation. The seated measurements were repeated after 4 weeks of oral diuretic therapy with hydrochlorothiazide (25 mg/d). RESULTS: The variation in the aldosterone-renin ratio was strongly and inversely dependent on PRA (R2=0.71; P<.001). When subjects changed position from supine to seated, the increase in mean +/- SD PRA (from 1.18 +/- 1.06 to 1.31 +/- 1.19 ng x mL(-1) x h(-1); P<.001) was associated with an increase in the mean ratio (from 18.6 +/- 52.8 to 25.8 +/- 38.1 h x 10(2); P<.001), whereas the increase in mean +/- SD PRA in response to diuretic therapy (from 1.31 +/- 1.19 to 2.72 +/- 2.67 ng x mL(-1) x h(-1); P=.007) was associated with a decrease in the mean ratio (from 25.8 +/- 38.1 to 16.4 +/- 31.6 h 10(2); P<.001). CONCLUSION: In patients with previously diagnosed essential hypertension, calculation of the aldosterone-renin ratio does not provide a renin-independent measure of circulating aldosterone that is suitable for determining whether PAC is elevated relative to PRA. Because elevation of the aldosterone-renin ratio is predominantly an indicator of low PRA, its perceived value in screening for primary aldosteronism most likely derives from additional diagnostic tests being done in patients with low-renin hypertension.     

The effect of dexamethasone on the control of plasma aldosterone concentration in normal recumbent man.

In order to evaluate the control of the circadian rhythm of plasma aldosterone concentration in man, plasma aldosterone, cortisol, sodium and potassium concentrations, and plasma renin activity (PRA) were measured in samples obtained at 20-minute intervals from 0200 to 0800 in sodium repleted (180 mEq. per day of diet) and sodium depleted (22 mEq. per day of diet) normal subjects. During sodium replete studies, plasma aldosterone and cortisol concentrations were significantly correlated (p greater than 0.01) in all 4 subjects. Plasma aldosterone also correlated with PRA (p greather than 0.01) in 2 subjects and with potassium (p greater than 0.01) in one. Episodic increases in plasma aldosterone concentration were observed despite suppression of ACTH by dexamethasone treatment. Plasma aldosterone concentrations were significantly correlated with PRA (p greater than 0.05 and p greater than 0.01) in only 2 of 4 subjects under these conditions. Following sodium restriction, plasma aldosterone concentrations were not significantly correlated with plasma cortisol and only infrequently with either PRA or potassium. When dexamethasone was administered during the low sodium diet, correlations with PRA (p greater than 0.001) were seen in 2 of 3 subjects and with potassium (p greater than 0.01) in 1 of 3 subjects. There was no significant correlation between plasma aldosterone and sodium concentration during any of the studies. These results are compatible with the concept that the relative importance of PRA, ACTH, and potassium in inducing changes in aldosterone production during the early morning hours is partially dependent upon dietary sodium, but also varies between individuals studied during similar sodium diets. The episodic alterations of plasma aldosterone concentration continued after ACTH was suppressed by dexamethasone pretreatment. These changes, in the absence of a consistent significant correlation with PRA and sodium and potassium concentrations, further suggest that another factor(s) may be important in controlling aldosterone production in recumbent normal subjects.     

不同体位肾素活性变化值对原发性醛固酮增多症鉴别诊断的价值

目的评估不同体位肾素活性变化值在高血压患者中诊断原发性醛固酮增多症(PA)的效能。 方法研究对象为2010年1月至2012年12月新疆维吾尔自治区人民医院高血压科收治的307例需要行继发性高血压筛查的高血压病患者。所有患者已行常规坐位肾素、醛固酮测定及立位、坐位、卧位肾素活性(PRA)、醛固酮测定、常规生化检测及人体学测量。满足坐位醛固酮/PRA值≥554 pmol/L·[μg/ (L·h)]^－1并且盐水输注试验后醛固酮≥277 pmol/L的患者被定义为PA组,其余患者为非PA组。使用四格表计算相关指标的敏感度、特异度等。 结果PA组与非PA组立位、坐位、卧位三种体位PRA比较,PA组[0.61 μg/(L·h),0.62 μg/(L·h),0.31 μg/(L·h)]低于非PA组[1.42 μg/(L·h),1.18 μg/(L·h),0.51 μg/(L·h)],差异有统计学意义(F＝11.465,12.052,10.296;P＝0.001);PA组与非PA组体位变换后PRA差值比较,PA组立卧位PRA差值[0.24 μg/(L·h)]低于非PA组[0.78 μg/(L·h)],差异有统计学意义(F＝8.303,P＝0.004);立位后PRA<1.0 μg/(L·h)或立卧位PRA差值<0.6 μg/(L·h)单项指标诊断PA的敏感度分别为64%及70%,特异度分别为62%及68%,阴性预测值分别是91%及93%;立位后PRA<1.0 μg/(L·h),联合立卧位PRA差值<0.6 μg/(L·h)诊断PA,其敏感度为45%,特异度为88%。 结论利用体位变换后PRA的变化值诊断PA效能较低,但有排除PA的临床价值,此试验患者配合度高,为生理性刺激试验,可安全有效地鉴别PA,联合试验后相关指标对诊断PA有临床参考价值。     

The Renin--Angiotensin--Aldosterone System in Decompensated Cirrhosis: Its Activity in Relation to Sodium Balance

Plasma renin activity (PRA), plasma renin concentration (PRC),plasma angiotensin II concentration (All), plasma and urinaryaldosterone (PA, UA) and urinary sodium excretion (UNaV) weremeasured in 51 normal controls, 16 patients with decompensatedcirrhosis (i. e. ascites and/or oedema present) in sodium equilibrium(Group 1) and 13 patients with decompensated cirrhosis in aphase of active sodium retention (Group 2). In Group 1 the meansupine and erect values, although lower, were not significantlydifferent from controls. In Group 2 the mean values were significantlyelevated, but several individual values were within the normalrange; there were significant direct relationships between plasmarenin activity and plasma renin concentration (r = 0.85, p <0.001 erect), plasma renin concentration and plasma angiotensinII concentration (r = 0.86, p < 0.001 erect), and plasmaangiotensin II concentration and plasma aldosterone (r = 0.70,p < 0.01 erect). In Group 2 there was an inverse correlationbetween urinary sodium excretion and both urinary aldosterone(r = – 0.50) and erect plasma aldosterone (r = –0.36) but, perhaps because of the narrow range of sodium excretionrates, significance was not reached. The normal values in Group 1 indicate that hyperaldosteronismis not essential for the maintenance of established ascites,but do not exclude a role for aldosterone in the control ofsodium excretion if it is accepted that renal tubular sensitivityto aldosterone is increased in these patients. In Group 2, theraised mean plasma and urinary aldosterone levels and the trendtowards an inverse relationship with urinary sodium excretionsuggests a role for aldosterone in the active retention of sodium.It appears that stimulation of the renin-angiotensin systemis the major factor in the elevation of plasma aldosterone;there was no relationship between plasma aldosterone and eitherplasma sodium or potassium levels. The mechanism of renin hypersecretionis unclear but this may represent part of a sympatheticallymediated response in order to maintain blood pressure. The closerelationship between plasma renin activity and plasma reninconcentration indicates that the former is a valid measure ofcirculating renin levels in cirrhosis, despite low renin-substratelevels.