A delayed suppression of the renin-aldosterone axis following saline infusion in human hypertension

The purpose of this study was to compare the acute suppressibility of the renin-angiotensin-aldosterone (RAA) axis in normotensive (n = 23) and essential hypertensive (n = 62) subjects. Only those hypertensive subjects with normal plasma renin activity (PRA) levels (sodium restricted, upright) were included in the study. Acute suppression of the RAA axis was determined by measuring PRA, plasma angiotensin II (A II), and plasma aldosterone (PA) at frequent intervals during the infusion of isotonic saline (500 ml/hour for 6 hours). Although all parameters fell significantly from control levels by 20-30 minutes in the normotensive subjects, we found that 60% of the hypertensive subjects showed no significant decline in PRA or PA until 120-240 minutes after beginning the infusion. The other hypertensive subjects showed normal RAA suppression. In addition, while there were no significant differences between the three groups in control PRA or PA levels, we found that the PA levels from 30 to 240 minutes during the saline were significantly higher (P less than 0.01) in the hypertensive subjects with delayed suppression. That there were two distinct populations in the hypertensive group was suggested by the bimodality of the frequency response curve, with peaks occurring at 30 and 240 minutes. These studies indicate an abnormality in the acute suppression of the RAA axis in a substantial proportion of subjects with normal renin essential hypertension. Since previous studies in normal subjects have reported that the early phase of response to saline infusion is related to the sodium ion per se and not to intravascular volume expansion, we have come to the conclusion that the present data are consistent with the hypothesis that the delayed suppression hypertensive group has a diminished ability to respond to the sodium ion.     

The therapeutic effect of hypertonic solutions on the changes in the effective circulating plasma volume in acute necrotizing pancreatitis in rats

While hypovolemia or hypovolemic shock is dominant in the early stage of severe acute pancreatitis, there have been few studies on the effects of hypertonic solutions in the management of this disease. We conducted this study to evaluate the therapeutic effects of hypertonic saline solutions (HS) on the course of severe acute pancreatitis in rats. Pancreatitis was induced in male Wistar rats by injecting a 5% solution of sodium taurocholate into the biliopancreatic duct. The effective circulating plasma volume (ECPV) was measured using radioiodinated [125I]bovine serum albumin. Samples of blood and of ascitic fluid were obtained 3, 6, and 12 h after the onset of pancreatitis. Lactated Ringer's solution (LR) and HS were administered consecutively for 3 h beginning 3 h after the induction of pancreatitis. ECPV was measured 6 h after the onset of pancreatitis. The survival rates were investigated for up to 10 days. The mean ECPV decreased significantly from 24.9 +/- 1.1 ml/kg before disease onset to 11.5 +/- 1.3 ml/kg 6 h postoperatively. LR failed to achieve a normal value for ECPV even following a 150 ml/kg infusion. HS200 and HS300 restored the ECPV to the normal level, and with smaller volumes infused. All rats in the untreated group died within 3 days. LR and HS improved the survival rates, with the infusion of HS200, 100 ml/kg, thus attaining a 45% survival at 10 days.     

In familial hyperaldosteronism type I, hybrid gene-induced aldosterone production dominates that induced by wild-type genes

We compared the aldosterone-producing potency of the angiotensin II-sensitive wild-type aldosterone synthase genes and the ACTH-sensitive hybrid 11 beta-hydroxylase/aldosterone synthase gene by examining aldosterone, PRA, and cortisol day-curves (2-hourly levels over 24 h) in patients with familial hyperaldosteronism type I, before and during long-term (0.8-13.5 yr) glucocorticoid treatment. In 8 untreated patients, PRA levels were usually suppressed, and aldosterone correlated strongly with cortisol (r = 0.69-0.99). Fourteen studies were performed on 10 patients receiving glucocorticoid treatment that corrected hypertension, hypokalemia, and PRA suppression in all. ACTH was markedly and continuously suppressed in 6 studies, 3 of which demonstrated strong correlations between aldosterone and PRA (r = 0.77-0.92). ACTH was only partially suppressed in the remaining 8 studies; aldosterone correlated strongly: 1) with cortisol alone in 5 (r = 0.71-0.98); 2) with cortisol (r = 0.90) and PRA (r = 0.74) in one; 3) with PRA only in one (r = 0.80); and 4) with neither PRA nor cortisol in one. Unless ACTH is markedly and continuously suppressed, aldosterone is more responsive to ACTH than to renin/angiotensin II, despite the latter being unsuppressed. This is consistent with the hybrid gene being more powerfully expressed than the wild-type aldosterone synthase genes in familial hyperaldosteronism type I.     

Effect of administered potassium on the renin-aldosterone axis in young blacks compared with whites

BACKGROUND: We had observed previously that the aldosterone excretion rate and plasma aldosterone concentration were lower for black children than they were for white children. We did not know whether this was secondary to a lower intake of potassium or to suppression of the renin-angiotensin system in blacks. OBJECTIVE: To test the hypothesis that the secretion of aldosterone in response to potassium would be different in blacks than in a control group of whites. DESIGN: Black and white subjects were selected on the basis of their having aldosterone excretion rates that were in the lowest quartile for the entire original cohort. Since the blacks typically had lower aldosterone excretion rates than did the whites, the black participants were represented primarily by those with average rates of aldosterone production among blacks, whereas the whites were represented by those with the lowest aldosterone production rates among whites. The protocol consisted of a placebo-controlled, randomized cross-over study design. METHODS: Twelve blacks and 12 whites, aged 14.1 +/- 1.6 (mean +/- SD) and 15.4 +/- 2.1 years, respectively, were allocated randomly to double-blind treatment either with placebo or with 40 mmol/day potassium chloride for 7 days and then the alternate treatment Measurements of the plasma renin activity (PRA), plasma aldosterone concentration, and urinary aldosterone excretion were performed in an inpatient research unit at the end of the treatment. The blood pressure was monitored for 24 h. RESULTS: Treatment with potassium increased the plasma aldosterone concentration (P = 0.0006) and the urinary excretion of aldosterone (P = 0.0002) significantly both for blacks and for whites. There was no significant racial difference in the response to potassium. The PRA was overall 1.605-fold lower in the blacks than it was in the whites (P = 0.0124). The lowest PRA levels, such as those in the blacks when they were supine, tended to be increased with the potassium treatment. The blood pressure did not change significantly with the potassium supplement for either racial group. CONCLUSIONS: After we had supplemented the intake of potassium, aldosterone production increased in the blacks and in the control group of whites to the same extent The potassium treatment appeared to increase lower PRA levels. A lower intake of potassium could at least partially account for the suppression of the renin-aldosterone system in blacks.     

An evaluation of antiseptics used for hand disinfection in wards

The diurnal rhythm of plasma aldosterone concentration (PA), plasma renin activity (PRA), plasma cortisol (PC) and serum growth hormone (GH) were examined in 5 cases of normotensive acromegaly and the results were compared with the observations in normal subjects. Moreover, the response of PA to angiotensin-II infusion was studied in 6 cases of normotensive acromegaly. A normal diurnal rhythm with the lowest values in the evening or midnight and the highest values in the morning was observed in 3 of 5 cases in PA and 3 of 4 cases in PC. On the other hand, no apparent rhythm of GH was observed in any cases and that of PRA in 4 of 5 cases. Although there was a significant positive correlation between PA and PC, no significant correlation was demonstrated between PA and PRA. The response of PA to angiotensin-II fusion was significantly suppressed in normotensive acromegaly as compared to the normal subjects in spite of normal levels of PRA except for 1 case. The above observations were interpreted to suggest that the aldosterone regulation system is slightly altered in a certain number of patients with normotensive acromegaly in contrast to the normal subjects in which PRA is the main contributing factor. The low PA and suppressed response of PA toangiotensin-II infusion may suggest the defective action of angiotensin-II infusion on the adrenal gland.     

Cromakalim suppresses hypertonic saline-induced renal vasoconstriction in anaesthetized dogs

1. Intrarenal arterial infusion of hypertonic saline (HS) transiently increased and then gradually reduced renal blood flow (RBF) in anaesthetized dogs. Glomerular filtration rate (GFR) but not filtration fraction decreased at the end of the infusion. 2. In the presence of a potassium channel opener cromakalim (0.3 microgram/kg per min), HS infusion failed to reduce RBF; the initial increase in RBF was maintained throughout the infusion. Since cromakalim also prevented the decrease in GFR, HS infusion lowered filtration fraction. 3. The results suggest that cromakalim inhibits both pre-and postglomerular vasoconstriction induced by HS infusion.     

The effects of dietary sodium on the diurnal activity of the renin-angiotensin-aldosterone system and the excretion of urinary electrolytes

Diurnal variations of five normal men were tested over three 24 h consecutive periods. The first experiment began at 0900 h after the subjects had fasted for 12 h and a normal sodium diet of about 70-80 mEq was given at 0900 h, 1200h, and 1630 h (total of about 220 mEq of Na). Significant variations in the plasma renin activity (PRA), in the plasma aldosterone (PA), and in the urinary Na and K outputs were found. The second experiment began at 1200 h with the first feeding time at 2100 h after fasting about 24 h and the subjects were given a normal sodium diet as in the first experiment, but with the meals given at 2100 h, 2400 h, and 0430 h. The diurnal variations in PRA, plasma aldosterone, and urinary electrolytes disappeared. From this study, it appears that the diurnal variation in urinary electrolyte excretion is a factor of the diurnal variation in PRA and plasma aldosterone. The diurnal variation in PRA and plasma aldosterone are related to the timing of sodium ingestion.     

Effect of blockade of angiotensin II on blood pressure, renin and aldosterone in cirrhosis

1-Sar-8-ala angiotensin II (saralasin) was infused intravenously in graded doses of from 0.1 to 10 mug/kg/min to five patients with cirrhosis and ascites after three days of restricted sodium intake. In each patient blockade of AII by saralasin produced a marked fall in blood pressure, a rise in plasma renin activity (PRA) and plasma renin concentration (PRC) and, in four of the five, a fall in plasma aldosterone (PA). The rise in PRA and PRC correlated poorly with changes in blood pressure. The effects of saralasin rapidly reversed after cessation of the infusion. Plasma volume was normal or high in each case. Three patients were mildly hypotensive in the control state, and all five were resistant to the pressor effect of infused AII. After three days of salt loading, the above effects of saralasin were diminished but not abolished. In four normal subjects, after salt depletion, saralasin infusion induced qualitatively similar but much smaller changes in blood pressure, PRA and PRC. In two cirrhotic patients without ascites, after salt depletion, saralasin infusion caused a rise in blood pressure with no significant changes in PRA, PRC or PA. These results provide evidence that in patients with cirrhosis and ascites circulating AII is active in support of blood pressure, in direct suppression of renal renin release, and in stimulation of aldosterone release.     

Chemokine receptor CXCR4 expression in endothelium

The aim of the present study was to study the sensibility in the area of saline-induced muscle pain. In three experiments, ten subjects were exposed to computer-controlled infusion of 0.5 ml isotonic (0.9%) or hypertonic (9%) saline into the anterior tibial muscle. The pain intensity was assessed on a visual analogue scale (VAS). The pain threshold (PT) to pressure and electrical stimulation in muscle and subcutaneous tissues was determined. Three experiments were performed in which infusion of hypertonic saline produced significantly higher VAS scores than isotonic saline. In all three experiments, there was no significant difference in PT obtained after infusion of isotonic saline compared with infusion of hypertonic saline. In experiment 1, the PT was determined at the infusion site and 4 cm from the infusion site. At the infusion site, the pressure PT decreased (-19 +/- 2%) 1, 3, 5, 7 and 9 min after infusion of isotonic and hypertonic saline, but remained unchanged 4 cm from the infusion site. The intramuscular electrical PT at the infusion site and 4 cm from the infusion site increased significantly (29 +/- 6%) 5, 7 and 9 min after saline infusion. In experiment 2, the pressure PT and the intramuscular electrical PT were recorded after two infusions of saline separated by 1 day. The day after the first infusion, the pressure PT was decreased compared with the PT before the first infusion, but the electrical PT was not affected. Moreover, the hypertonic saline infusion given on the second day produced significantly higher (130 +/- 50%) VAS scores than the infusion given on the first day. In experiment 3, the PT was determined in the subcutaneous tissue, but no significant effects of saline infusion were found. The present placebo-controlled experiments failed to show muscular or subcutaneous hyperalgesia after saline-induced muscle pain per se.     

Effect of increasing doses of hypertonic saline on mucociliary clearance in patients with cystic fibrosis

BACKGROUND: Patients with cystic fibrosis are known to have decreased mucociliary clearance. It has previously been shown that inhalation of a 7.0% solution of hypertonic saline significantly improved mucociliary clearance in a group of adult patients with cystic fibrosis. The aim of this study was to measure the response to increasing concentrations of inhaled hypertonic saline. METHODS: Ten patients (seven men) of mean (SE) age 22 (4) years and mean forced expiratory volume in one second (FEV1) 52.0 (6.7)% predicted completed the study. Mucociliary clearance was measured using a radioaerosol technique for 90 minutes after the interventions which comprised 0.9% NaCl + voluntary cough (control), 3.0% NaCl, 7.0% NaCl, and 12% NaCl. RESULTS: There was a significant increase in the amount of activity cleared from the right lung with all concentrations of hypertonic saline (HS) compared with control. The amount cleared at 90 minutes on the control day was 12.7% (95% confidence interval (CI) 9.8 to 17.2) compared with 19.7% (95% CI 13.6 to 29.5) for 3% HS, 23.8% (95% CI 15.9 to 36.7) for 7% HS and 26.0% (95% CI 19.8 to 35.9) for 12% HS. The improvement in mucociliary clearance was not solely due to coughing as the number of coughs recorded on the control day exceeded that recorded on any other day. The hypertonic saline did not induce a clinically significant change in FEV1. CONCLUSIONS: Within the range of concentrations examined in this study, the effect of hypertonic saline appears to be dose dependent. Inhalation of hypertonic saline remains a potentially useful treatment for patients with cystic fibrosis.     

Effect of sodium restriction and angiotensin II infusion in Bartter's syndrome

Five patients with Bartter's syndrome were investigated. Sodium restriction (less than 10 mEq/day for at least 5 days) showed a renal sodium wastage in only two patients (I and II) in spite of increased aldosterone secretion rate (from 151-427 to 680-842 mug/day). The effect of angiotensin II (A II) 80ng/kg/min for 30-180 min, on plasma renin activity (PRA), plasma aldosterone, and urinary sodium excretion was compared with the effect of a previous infusion of 5% dextrose given at the same rate, 0.5 ml/min for 1 hr. A II infusion resulted in increased plasma aldosterone levels: from 236-330 pg/ml to 800-881 pg/ml in 30 min. This increase was also observed in patient II (from 139 to 600 pg/ml). PRA was decreased by A II infusion (from 1,142-2,462 to 121-1,625 ng/liter/min). In patient IV, this decrease in PRA was also observed when he was on a salt-restricted diet (from 1,934 to 370 ng/liter/min); but the minimal PRA was still higher (370 ng/liter/min) than with a normal diet (121 ng/liter/min). In no case could normal PRA level be obtained. A II infusion induced an increase in urinary sodium excretion only in the two patients with renal sodium wastage (from 80-90 to 265-230 muEq/min in 30 min). Urinary sodium excretion decreased in the other patients from (37.5-213 to 4.30-46 muEq/min) and fractional sodium excretion was reduced in patient V (from 0.56% to 0.45% at 30 min and to 0.29% at 120 min). No significant change with A II infusion was observed in patient IV when he was on a sodium-restricted diet (from 1 to 2.5 muEq/min in 30 min). Urinary potassium excretion was similar to sodium excretion. No change was observed in plasma potassium and sodium.     

Effects of nonesterified fatty acids on glucose metabolism after glucose ingestion

Impaired suppression of plasma nonesterified fatty acids (NEFAs) after glucose ingestion may contribute to glucose intolerance, but the mechanisms are unclear. Evidence that insulin inhibits hepatic glucose output (HGO), in part by suppressing plasma NEFA levels, suggests that impaired suppression of plasma NEFA after glucose ingestion would impair HGO suppression and increase the systemic delivery of glucose. To test this hypothesis, we studied glucose kinetics (constant intravenous [3-3H]glucose [0.4 microCi/min], oral [1-14C]glucose [100 microCi]), whole-body substrate oxidation, and leg glucose uptake in eight normal subjects (age, 39 +/- 9 years [mean +/- SD]; BMI, 24 +/- 2 kg/m2) in response to 75 g oral glucose on two occasions. In one study, plasma NEFAs were prevented from falling by infusion of 20% Liposyn (45 ml/h) and heparin (750 U/h). Plasma glucose rose more rapidly during lipid infusion (P < 0.05), and mean levels tended to be higher after 120 min (6.45 +/- 0.41 vs. 5.81 +/- 0.25 SE, 0.1 < P < 0.05, NS); peak glucose levels were similar. Total glucose appearance (Ra) was higher during lipid infusion due to a higher HGO (28.4 +/- 1.0 vs. 21.2 +/- 1.5 g over 4 h, P < 0.005). Total glucose disposal (Rd) was also higher (88 +/- 2 vs. 81 +/- 3 g in 4 h, P < 0.05). Plasma insulin rose more rapidly after glucose ingestion with lipid infusion, and leg glucose uptake was 33% higher (P < 0.05) during the 1st hour. During lipid infusion, subjects oxidized less glucose (47 +/- 3 vs. 55 +/- 2 g, P < 0.05) and more fat (7.1 +/- 0.8 vs. 3.9 +/- 0.9 g, P < 0.02). In summary, 1) impaired suppression of NEFAs after oral glucose impairs insulin's ability to suppress HGO, and 2) in normal subjects the greater insulin response compensates for the increased systemic glucose delivery by increasing peripheral glucose Rd.     

The importance of studying the renin-angiotensin-aldosterone system in essential arterial hypertension in clinical practice. Activity of the renin-angiotensin-aldosterone system during treatment of hypertension with ACE-inhibitors and beta blockers

The authors assessed in 20 subjects with mild or medium severe arterial hypertension basal and stimulated values of plasma renin activity (PRA) and aldosterone before onset of treatment and after 6-week therapy with enalapril (ENAP KRKA) or metoprolol (Vasocardin Slovakofarma). PRA and aldosterone secretion was stimulated by a vertical position and by administration of 40 mg furosemide by the i.v. This test proved suitable for assessment of secondary arterial hypertension in different forms of primary hyperaldosteronism and for expressing suspicion of renovascular hypertension and hypertension with affection of the renal arteries resp. Based on PRA levels, arterial hypertension can be divided into normorenin, high-renin and low-renin hypertension. This classification is, however, of no value for selection of treatment and the prognosis of hypertension. Each level of PRA can be associated with three different aldosterone levels. PRA and aldosterone did not correlate with urinary K, Na excretion nor with blood pressure. During treatment with ACE inhibitor PRA rose while basal as well as stimulated aldosterone levels declined. After administration of betablockers basal as well as stimulated PRA and aldosterone levels declined.     

The acute and 24-hour modifications to the atrial natriuretic factor in patients who have undergone mitral valvuloplasty. The hemodynamic and echocardiographic correlations

BACKGROUND: The recent introduction of percutaneous transvenous mitral valvuloplasty (PTMV) for the treatment of mitral stenosis (MS) has provided a unique human model for the study of short-term changes in ANF secretion before and after a reduction in left atrial pressure. This study was designed to investigate the effect of a short-term reduction in left atrial pressure and volume, as determined by echocardiographic study, on ANF and other neurohumoral factor plasma levels (renin and aldosterone). MATERIALS AND METHODS: 10 patients in III FC NYHA, with normal sinus rhythm and MS underwent PTMV. Hemodynamic parameters were measured immediately before and after (20-30 minutes) PTMV. Plasma levels of ANF, aldosterone and plasma renin activity (PRA) were obtained before (24 h) and after (2 h and 24 h) valvuloplasty; echocardiographic left atrial size before (24 h) and 24 h after PTMV. RESULTS: Immediately after PTMV mean left atrial (LA) pressure decreased from 22.3 +/- 6.8 mmHg to 10.0 +/- 2.4 mmHg (p < 0.01); mitral valve area (MVA) increased from 0.99 +/- 0.28 cm2 to 2.17 +/- 0.26 cm2 (p < 0.01). 24 hours after PTMV on echocardiography, LA systolic volume decreased from 59.5 +/- 16.9 cm3 to 42.3 +/- 8.3 cm3 (p < 0.01), LA diastolic volume from 82.6 +/- 15.8 cm3 to 66.5 +/- 12.6 cm3 (p < 0.01), and LA diameter from 48.1 +/- 7.5 mm to 39.2 +/- 4.4 mm (p < 0.01). ANF plasma levels before PTMV were 64.0 +/- 36.9 fmol/ml; 2 and 24 hours after PTMV they fell to 34.2 +/- 21.6 fmol/ml (p < 0.01) and to 20.3 +/- 21.0 fmol/ml (p < 0.01), respectively. PRA values were 15.7 +/- 13.2 ng/ml/h before PTMV; 2 and 24 hours after PTMV they increased to 17.5 +/- 23.2 ng/ml/h (NS) and to 22.3 +/- 16.8 ng/ml/h (p < 0.01). The aldosterone plasma levels were 43.2 +/- 27.9 ng/dl before PTMV and 47.3 +/- 35.8 ng/dl (NS) and 45.3 +/- 28.0 ng/dl (NS) 2 and 24 hours after PTMV. CONCLUSIONS: These results indicate that LA "de-stretching" due to the MVA increase and LA pressure decrease, leads to an abrupt reduction of ANF secretion. According to other studies, PRA increases immediately after PTMV, with a further increase 24 hours after PTMV.     

Regulation of 18-oxocortisol and 18-hydroxycortisol by the renin-angiotensin system and ACTH in man

Based on urinary excretion studies the secretion of the cortisol derivatives, 18-oxocortisol and 18-hydroxycortisol are believed to be regulated by ACTH and to a lesser degree by the renin-angiotensin system. Plasma concentrations of 18-oxocortisol and 18-hydroxycortisol were measured during the simultaneous activation of the renin-angiotensin system and inhibition of ACTH secretion. Five healthy male subjects consuming a sodium diet ad libitum were studied. Blood was drawn at 0800 h after 1 h in the supine position. In the first set of experiments, the subjects remained in the supine position from 0800 to 1000 h with or without the oral administration of 2 mg dexamethasone at 0800 h. In the second set of experiments the subjects were placed in the upright position after drawing the 0800 h sample. The subjects were studied with and without dexamethasone administered at 0800 h. Blood was drawn again at 1000 h. Plasma levels of 18-oxocortisol, 18-hydroxycortisol, ACTH, plasma renin activity (PRA), cortisol, aldosterone and 18-hydroxycorticosterone were measured by radioimmunoassay. None of these parameters changed during the 2 h in the supine position. 18-Oxocortisol, 18-hydroxycortisol, aldosterone, 18-hydroxycorticosterone and PRA increased, but ACTH and cortisol did not change when the subjects were placed in the upright position. After dexamethasone administration, 18-oxocortisol, 18-hydroxycortisol, cortisol, aldosterone and 18-hydroxycorticosterone decreased in the supine position and no increase occurred in 18-oxocortisol, 18-hydroxycortisol and 18-hydroxycorticosterone in the upright position. PRA and aldosterone increased and ACTH and cortisol decreased in these subjects. 18-Oxocortisol and 18-hydroxycortisol were more dependent on ACTH regulation and less on the renin-angiotensin system than aldosterone.     

Plasma levels of atrial natriuretic peptide and brain natriuretic peptide following intravenous saline infusion in oedematous chronic obstructive pulmonary disease and non-oedematous chronic obstructive pulmonary disease

Some patients with chronic obstructive pulmonary disease (COPD) develop oedematous COPD (oCOPD) with peripheral oedema and have a poor prognosis. The cause of the fluid retention is poorly understood but could be due to defective release of a natriuretic factor. We investigated this hypothesis by measuring levels of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) before and after a 0.1 ml/kg/min 2.7% saline infusion in 6 patients with hypoxemic COPD but no history of oedema and 7 COPD patients with oCOPD. Vasopressin, aldosterone, plasma and urinary urea and electrolytes and osmolality were measured. Arterial blood gases and spirometry were also recorded. The two groups were similar in terms of age, weight, PaO2, PaCO2 and FVC. FEV1 was significantly lower in the oCOPD group. The oCOPD group excreted less urine (202 +/- 23 vs. 364 +/- 48 ml; p < 0.05) and less sodium (32 +/- 3 vs. 68 +/- 9 mmol/l; p < 0.01) as a percentage of the saline load given (18 +/- 2 vs. 30 +/- 4%; p < 0.05). Pre-infusion BNP and ANP levels were similar in both groups. BNP and ANP had an exaggerated increase in the oCOPD group on saline loading. In the oCOPD group, ANP levels were significantly greater 1 h after the saline load compared to the pre-infusion values (30 +/- 7 vs. 11 +/- 2; p < 0.05). BNP did not reach significantly greater levels than baseline values until 3 h after the infusion had ended (45 +/- 6 vs. 27 +/- 2; p < 0.05). At 1 h after the saline load, BNP and ANP levels were significantly greater in the oCOPD group (BNP 32 +/- 2 vs. 24 +/- 1; p < 0.01 and ANP 30 +/- 7 vs. 7 +/- 2; p < 0.05) when compared to COPD controls. BNP levels remained significantly different from the COPD control group 3 h after the infusion ended (45 +/- 6 vs. 26 +/- 2; p < 0.05). Although aldosterone levels were greater in the oCOPD group before the saline infusion, the hormone level was suppressed appropriately by the infusion. In conclusion, the cause of oedema in oCOPD and the inability to excrete a saline load is not due to a failure of release of BNP or ANP.     

Comparison of bronchial challenge with ultrasonic nebulized distilled water and hypertonic saline in children with mild-to-moderate asthma

There is still controversy about the most suitable method to measure bronchial hyperresponsiveness in children. In epidemiological surveys, nonisotonic aerosols are being used increasingly for bronchial provocation testing. Our aim was to study the acceptability, safety and correlation between two published bronchial challenge tests. Two standardized protocols--the inhalation of hypertonic saline (HS) and ultrasonically-nebulized distilled water (UNDW)--were performed in 36 children: 19 patients with the clinical diagnosis of mild-to-moderate asthma (7-12 yrs of age), and 17 control subjects (8-18 yrs of age). HS challenge involved stepwise inhalation of 4.5% saline (for 0.5, 1, 2, 4 and 8 min), whereas challenge with UNDW was performed as a single step protocol with 10 min inhalation of cold UNDW. Asthma medication was withheld prior to challenge testing. Thirty five subjects completed both challenge tests (one asthmatic patient did not return after UNDW challenge) in random order within a 7 day time interval. For HS a > or = 15% reduction in forced expiratory volume in one second (FEV1) from baseline was considered a positive response, and for UNDW a > or = 10% decrease. In 13 of the 19 asthmatic patients, but in none of the controls, a positive response was observed for UNDW. Fifteen out of 18 patients and one control subject had a positive response to HS. Twelve out of 18 asthmatic children responded to both challenges, three responded only to HS and three had no response to either challenge. There was a negative correlation between log provocative dose causing a 15% reduction in FEV1 (PD15) after HS and the maximum fall in FEV1 after UNDW (rs = -0.63; p < 0.005). The HS challenge had a lower acceptability than challenge with UNDW due to the unpleasant salty taste of HS. However, this did not inhibit the completion of the tests in any subject. The results of this study suggest a good correlation between response to hypertonic saline and ultrasonically-nebulized distilled water in children with mild-to-moderate asthma. A multiple step protocol might be safer when applied in field studies involving children.     

Biological activity of des-Asp1-,Ileu8-angiotensin II (Ileu8-angiotensin III) in man

Biological activity of ileu8-angiotensin III (AIIIA) was studied in man. In 5 normal men intravenous infusion of 200 ng/kg/min of AIIIA for 30 minutes from 0900 h had no effect on blood pressure (BP) but caused a decrease in plasma renin activity (PRA) and an increase in plasma aldosterone (PA). This dose did not inhibit pressor and steroidogenic actions of angiotensin II (AII) infused into the normal men at a rate of 20 ng/kg/min for 30 minutes. In 3 patients with Bartter's syndrome 260-1,200 ng/kg/ min of AIIIA infusion for 30 minutes from 0900 h had no effect on BP but caused decreases in PRA and PA. These results indicate that in man AIIIA has no pressor action and no antagonistic effect on pressor action of AII but has PRA-lowering and aldosterone-stimulating effects. Antagonistic effect of AIIIA on steroidogenic action of AII was also shown in patients with Bartter's syndrome but not in AII-treated normal men. This may be due to the difference of administered dose of AIIIA.     

Rebound increase of PAI-1 following local intra-arterial rt-PA infusion, a possible cause of reocclusion

We obtained normative data for plasma renin activity (PRA) and plasma aldosterone concentration from a biracial sample of 195 healthy, normotensive children and adolescents aged 10 to 18 years. The sample included 119 boys and 76 girls, of whom 103 were black and 92 were white. The mean PRA value (+/- SD) was 2.52 +/- 1.95 ng/ml per hour, with minimal and maximal values of 0.1 and 13.50 ng/ml per hour. The mean plasma aldosterone concentration was 12.56 +/- 8.59 ng/ml, with minimal and maximal values of 1.6 and 50.1 ng/ml. We also examined the effects of subject characteristics and electrolyte intake. The slope relating sodium excretion to PRA was negative and highly significant (slope = -0.01; p < 0.003). The slope relating PRA to plasma aldosterone concentration was positive and highly significant (slope = 1.59; p < 0.0001). We did not observe differences in either variable as a function of age, sex, race, or family history of hypertension. These results suggest that differences based on race and family history of hypertension observed in adults are not present in youth.     

Effect of bucladesine sodium on the plasma concentrations and urinary excretion of purine bases and uridine

To examine whether bucladesine sodium affects the plasma concentrations of purine bases (hypoxanthine, xanthine, and uric acid) and uridine, 100 mL of physiological saline containing bucladesine sodium (6 mg/kg weight) was administered intravenously to eight healthy subjects for 1 hour after overnight fast except for water. Blood was drawn 30 minutes before, and 30 minutes and 1 hour after the beginning of the infusion, and 1-hour urine was collected before and after the beginning of the infusion. Two weeks later, 100 mL of only physiological saline was administered under the same protocol. Bucladesine sodium decreased the plasma concentrations of hypoxanthine by 36% and by 37%, and of xanthine by 16% and 33%, and of uridine by 17% and 30%, 30 minutes and 1 hour after the beginning of the infusion, respectively, and increased the urinary excretion of hypoxanthine and uric acid by 140% and 30%, respectively, after the beginning of the infusion. However, it did not affect the plasma concentration of uric acid or the urinary excretion of xanthine, and the urinary excretion of uridine was less than 0.2 micromol/h before or after bucladesine sodium infusion. On the other hand, physiological saline alone did not affect any of the values described. These results suggest that bucladesine sodium acts on the secretory process of the renal transport of hypoxanthine, resulting in the increased urinary excretion of hypoxanthine, and further suggest that bucladesine sodium enhances the uptake of uridine in plasma to liver cells.