Plasma Atrial Natriuretic Peptide Concentrations Research Articles

The circulating renin-angiotensin system during treatment with metoprolol or captopril in patients with heart failure due to non-ischaemic dilated cardiomyopathy.

To investigate the effects of beta-blocker (metoprolol) or angiotensin-converting enzyme inhibitor (captopril) treatment on neurohormonal function in a randomized prospective study on patients with heart failure due to dilated cardiomyopathy. Fifty-four patients (42 men and 12 women, mean age 50 years) were studied. There were three patients in NYHA (New York Heart Association) functional class I, 32 patients in class II and 19 patients in class III. Measurements of plasma renin activity (PRA). plasma angiotensin II (A II) concentration and plasma atrial natriuretic peptide (ANP) concentration were made at rest and also in a subgroup (n = 32) during exercise. The urinary excretion of aldosterone was also determined. Investigations were performed at baseline, and after 3 and 6 months. Therapy was then stopped and the patients were re-investigated 1 month thereafter. The mean level of PRA was normal at baseline, reduced during therapy with metoprolol, and increased during therapy with captopril. The mean plasma concentration of A II was reduced during exercise and there was a trend towards a reduction even at rest in the metoprolol group, but not in the captopril group. The urinary excretion of aldosterone decreased in both groups. The mean plasma concentration of ANP was elevated at baseline and declined during exercise in the metoprolol group. In patients with dilated cardiomyopathy and only a partly activated renin-angiotensin system, both metoprolol and captopril reduced urinary excretion of aldosterone. Furthermore, metoprolol suppressed the exercise-induced increase in ANP, suggesting a favourable effect on ventricular performance.

Renin-aldosterone in elderly patients with hyperkalaemia under anaesthesia.

Elderly patients with hyperkalaemia often have low concentrations of plasma renin and aldosterone, perhaps secondary to reduced glomerular filtration and sympathetic insufficiency. The endocrine response to surgical stress and volume expansion during anaesthesia was studied in seven elderly patients with hyperkalaemia (mean age 87.7 +/- SD 5.3 years), 18 elderly patients without hyperkalaemia (86.5 +/- 5.5 years), and 18 younger patients (52.6 +/- 7.2 years) as controls. Base-line values, in hyperkalaemic elderly patients, for plasma renin activity and plasma aldosterone concentration were 0.8 +/- 0.3 ng mL-1 h-1 and 2.8 +/- 0.8 pg mL-1 respectively (significantly lower than in the younger patients), and 287 +/- 42 pg mL-1 for plasma atrial natriuretic peptide levels, which were significantly higher. The plasma renin activity and aldosterone concentrations in elderly patients with hyperkalaemia were at all times lower, but not significantly, than those of the elderly patients without hyperkalaemia. The atrial natriuretic peptide concentrations (351 +/- 48 pg mL-1) in the hyperkalaemic elderly were significantly higher 90 min after induction of anaesthesia than in the normokalaemic elderly (108 +/- 38 pg mL-1). Hormone concentrations in the hyperkalaemic patients did not change during anaesthesia, but plasma atrial natriuretic peptide concentrations increased significantly in the normokalaemic elderly, and plasma renin activity and aldosterone of the younger patients increased significantly during anaesthesia. These results indicate that plasma renin activity, and the concentrations of aldosterone and of atrial natriuretic peptide in elderly patients with hyperkalaemia are unresponsive to surgical stress and volume expansion.

Atrial natriuretic peptide and oxytocin induce natriuresis by release of cGMP.

Our hypothesis is that oxytocin (OT) causes natriuresis by activation of renal NO synthase that releases NO followed by cGMP that mediates the natriuresis. To test this hypothesis, an inhibitor of NO synthase, L-nitroarginine methyl ester (NAME), was injected into male rats. Blockade of NO release by NAME had no effect on natriuresis induced by atrial natriuretic peptide (ANP). This natriuresis presumably is caused by cGMP because ANP also activates guanylyl cyclase, which synthesizes cGMP from GTP. The 18-fold increase in sodium (Na+) excretion induced by OT (1 microgram) was accompanied by an increase in urinary cGMP and preceded by 20 min a 20-fold increase in NO3- excretion. NAME almost completely inhibited OT-induced natriuresis and increased NO3- excretion; however, when the dose of OT was increased 10-fold, a dose that markedly increases plasma ANP concentrations, NAME only partly inhibited the natriuresis. We conclude that the natriuretic action of OT is caused by a dual action: generation of NO leading to increased cGMP and at higher doses release of ANP that also releases cGMP. OT-induced natriuresis is caused mainly by decreased tubular Na+ reabsorption mediated by cGMP. In contrast to ANP that releases cGMP in the renal vessels and the tubules, OT acts on its receptors on NOergic cells demonstrated in the macula densa and proximal tubules to release cGMP that closes Na+ channels. Both ANP- and OT-induced kaliuresis also appear to be mediated by cGMP. We conclude that cGMP mediates natriuresis and kaliuresis induced by both ANP and OT.

Neurohumoral responses to a single haemodialysis in chronic renal patients.

The effect of volume reduction on vasoactive substances and their role in estimating dry weight in haemodialysis patients was studied. Plasma atrial natriuretic peptide (ANP), catecholamines, antidiuretic hormone, renin activity and serum aldosterone were measured in 12 patients before and after bicarbonate haemodialysis. Haemodynamical changes were registered and cardiac function and diameter of the inferior vena cava were measured by echocardiography before and after dialysis. Plasma concentration of ANP was significantly reduced by haemodialysis from 209 +/- 51 to 69 +/- 13 pg mL(-1) (n = 12, P < 0.05), whereas concentrations of the other hormones were unchanged. The change in the concentration of ANP did not have significant correlation with weight reduction. The concentration of ANP correlated positively with the diameter of the inferior vena cava (r = 0.70, P < 0.05) after dialysis, but not before dialysis. The concentration of ANP before or after haemodialysis or its change during dialysis did not correlate with any other biochemical parameter. The results show that plasma ANP level is decreased after volume reduction in patients with chronic renal failure, whereas other hormonal systems are unresponsive. However, plasma concentration of ANP seems to have no role in estimating dry weight in chronic haemodialysis patients.

Augmented expression of cardiac atrial natriuretic peptide system in hypertensive rats.

The present study was aimed at investigating the regulation of atrial natriuretic peptide (ANP) system in association with either enhanced or attenuated activity of the renin-angiotensin system (RAS). The cardiac tissue mRNA and peptide levels of ANP were measured in rats with two-kidney, one clip (2K1C) or deoxycorticosterone acetate (DOCA)-salt hypertension. Plasma renin concentration was increased in 2K1C hypertension along with increases of renin mRNA and protein contents in the clipped kidney. On the contrary, it was suppressed in DOCA-salt hypertension along with decreases of renin mRNA and protein contents in the remaining kidney. The plasma ANP concentration was similarly increased in both models of hypertension. The cardiac tissue ANP contents were not significantly changed, but the tissue ANP mRNA levels were upregulated in the hypertrophied heart in these two models of hypertension. It is suggested that the cardiac ANP system is transcriptionally enhanced by cardiac hypertrophy associated with hypertension, independent of the systemic RAS.

Augmentation of the cardiac natriuretic peptides by beta-receptor antagonism: evidence from a population-based study.

The present retrospective analysis of data derived from a population-based study examined the relationship between intake of beta-receptor antagonists and plasma concentrations of the cardiac natriuretic peptides and their second messenger. Beta-receptor antagonists are widely used for treatment of cardiovascular disease. In addition to direct effects on heart rate and cardiac contractility, recent evidence suggests that beta-receptor antagonists may also modulate the cross talk between the sympathetic nervous system and the cardiac natriuretic peptide system. Plasma concentrations of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP) and their second messenger cyclic guanosine monophosphate (cGMP) were assessed in addition to anthropometric, hemodynamic and echocardiographic parameters in a population-based sample (n = 672), of which 80 subjects used beta-receptor antagonists. Compared to subjects without medication, subjects receiving beta-receptor antagonists were characterized by substantially elevated ANP, BNP and cGMP plasma concentrations (plus 32%, 89% and 18%, respectively, p < 0.01 each). Analysis of subgroups revealed that this effect was highly consistent and present even in the absence of hypertension, left atrial enlargement, left ventricular hypertrophy or left ventricular dysfunction. The most prominent increase was observed in a subgroup with increased left ventricular mass index. By multivariate analysis, a statistically significant and independent association between beta-receptor antagonism and ANP, BNP and cGMP concentrations was confirmed. Such an association could not be demonstrated for other antihypertensive agents such as angiotensin-converting enzyme inhibitors or diuretics. Beta-receptor antagonists appear to augment plasma ANP, BNP and cGMP concentrations. The current observation suggests an important contribution of the cardiac natriuretic peptide system to the therapeutic mechanism of beta-receptor antagonists.

Increased renal ANP synthesis, but decreased or unchanged cardiac ANP synthesis in water-deprived and salt-restricted rats

Experiments were performed to examine the effect of water deprivation and salt restriction on ANP synthesis in the kidneys and hearts of normal rats. A 4-day water deprivation (WD) and 7-day salt restriction (SR; 0.01% NaCl) were performed in 12 and 14 rats, respectively. Atrial natriuretic peptide (ANP) mRNA expression in the kidney was assessed with reverse transcription-polymerase chain reaction coupled with Southern blot hybridization, while the ANP mRNA in the hearts was measured by Northern blot hybridization. ANP and angiotensin II concentrations in the extracted plasma were measured by radioimmunoassay. The molecular form of renal ANP-like protein was characterized by reverse phase-high-performance liquid chromatography (RP-HPLC). Renal outer and inner medullary ANP mRNA showed a respective 11-fold and ninefold increase in WD rats, and an eightfold and fivefold increase in SR rats as compared to corresponding control groups. Inversely, cardiac atrial ANP mRNA and plasma ANP were decreased in WD rats, whereas they did not change in the SR group. Plasma angiotensin II concentration increased in conjunction with the decrease of urine sodium excretion in both groups. RP-HPLC analysis revealed a 45% extraction of ANP in the WD rat kidneys, whereas only 3% ANP in the control kidneys migrated in a molecular form similar to cardiac atrial proANP. Our results demonstrate that water deprivation and salt restriction markedly enhance renal ANP mRNA, whereas water deprivation suppresses cardiac atrial ANP mRNA and plasma ANP concentrations. The current study indicates that renal ANP and cardiac atrial ANP appear to be two distinct systems regulated by different mechanisms and possibly exhibiting different intra-renal paracrine and systemic endocrine functions.

Value of cardiopulmonary exercise testing and big endothelin plasma levels to predict short-term prognosis of patients with chronic heart failure.

We tested the hypothesis that, in patients with stable heart failure, measuring big endothelin-1 (ET-1) plasma level at rest predicts short-term prognosis better than peak oxygen consumption (VO2max) at exercise. Cardiopulmonary exercise testing and evaluation of neurohumoral plasma factors are established tools to estimate survival in patients with heart failure. No data, however, exist comparing the prognostic value of both marker categories simultaneously. Two hundred twenty-six heart failure patients were studied in regard to a combined end point of death and prioritization for urgent cardiac transplantation within 1 year follow-up. During the study period 149 patients were without cardiac events (group A), 69 patients died or were urgently transplanted (group B) and 8 patients were alive after a nonurgent heart transplant operation. Norepinephrine (p < 0.0001), atrial natriuretic peptide (p < 0.001), big endothelin plasma levels (p < 0.0001 as well as workload, VO2max and achieved percentage of predicted peak oxygen consumption (pVO2max) (all p < 0.0001) differed significantly between groups A and B. In multivariate stepwise regression analysis, however, only big ET-1 plasma concentration (chi2=74.4, p < 0.0001), New York Heart Association function class (chi2=33.9, p < 0.0001), maximal workload (chi2=7.2, p < 0.01, and plasma atrial natriuretic peptide (ANP) concentration (chi2=4.6, p < 0.05) were independently related to outcome. Peak oxygen consumption or pVO2max did not reach statistical significance in this model. Event-free survival rates were significantly lower in patients with a big ET-1 level of 4.3 fmol/ml or more than with lower big ET-1 levels (p < 0.0001). We conclude that in patients with chronic heart failure who are stable on oral therapy measuring big ET-1 and ANP plasma levels may be a valuable noninvasive adjunct to improve the prognostic accuracy of detecting high risk patients compared with exercise testing alone.

Acute neurohumoral and cardiovascular effects of idarubicin in leukemia patients.

Idarubicin has been shown to have similar or superior antileukemic activity to daunorubicin with less cumulative cardiotoxicity. However, data of acute cardiovascular effects of idarubicin are scanty but may have clinical significance in predicting late cardiovascular complications. In the present study we evaluated prospectively acute neurohumoral and cardiovascular effects of idarubicin containing induction chemotherapy in 10 patients with newly diagnosed AML or MDS. Idarubicin was administered intravenously 12 mg/m2 on d 1, 3 and 5 as a part of the induction chemotherapy. Serial measurements of plasma atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were performed at baseline and the day following each idarubicin infusion. Echocardiography was performed to assess cardiac systolic and diastolic function. Signal averaged electrocardiography (ECG) was recorded to observe myocardial late potentials associated with possible myocardial injury. In addition, ambulatory ECG recording was performed to assess arrhythmias. Plasma concentrations of ANP increased from 18.2 +/- 1.5 pmol/l to 27.8 +/- 3.5 pmol/l (p = 0.011), to 30.2 +/- 3.0 pmol/l (p = 0.002) and to 40.8 +/- 6.0 pmol/l (p = 0.006) after the first, second and third doses of idarubicin, respectively. Similarly, plasma concentration of BNP increased from 6.2 +/- 1.9 to 9.0 +/- 1.8 pmol/l (p = 0.049) and 17.5 +/- 8.1 pmol/l (p = 0.203) after the first and third idarubicin infusion. Concomitantly, there was a trend towards an increase in left ventricular end diastolic diameter (LVEDD) (50.2 +/- 1.8 to 54.4 +/- 2.2 mm, p = 0.070). The increase in plasma BNP concentrations correlated significantly with the increase in LVEDD (r = 0.624; p = 0.002). No significant ECG changes or arrhythmias were associated with idarubicin infusions except in 1 patient who developed abnormal myocardial late potentials. Our results show that idarubicin causes acute neurohumoral activation associated with increased LVEDD indicating subclinical myocardial dysfunction. Whether these acute changes predict late clinical cardiomyopathy should be evaluated in prospective studies with larger number of patients and with higher cumulative anthracycline doses.

Effect of oxygen on pulmonary hemodynamics and incidence of atrial fibrillation after noncardiac thoracotomy

Objective: The mechanism of postthoracotomy atrial fibrillation (AF) could be related to right ventricular (RV) strain. The effect of oxygen on the occurrence of postoperative AF and on RV function was studied. Design: A prospective, randomized study. Setting: A university hospital. Participants: Twenty-four noncardiac thoracotomy patients. Interventions: At the end of the postoperative anesthesia care unit period, the patients were randomly allocated to receive 35% oxygen until either the third (P = prolonged group) or the first postoperative morning (S = short group). Measurements and Main Results: Measurement of hemodynamic variables using a thermodilution pulmonary artery catheter, oxygenation, concentration of plasma atrial natriuretic peptide (ANP) and Holter monitoring were started preoperatively and continued for the 3 postoperative days (PODs). Systolic RV pressure (systolic RVP) and pulmonary vascular resistance (PVR) increased postoperatively only in group S. Major changes in RV performance were not seen with echocardiography or the thermodilution method in any patient. Silent episodes of AF occurred in three patients (25%) in group P and in one patient (8%) in group S (not significant [NS]) without deviations in plasma ANP concentration. On each of the 3 PODs, all patients were exposed to 60% oxygen for 15 minutes. Systolic RVP decreased significantly during the exposure to 60% oxygen only in group S, but not in patients developing AF. Predictive factors for AF were a high preoperative PVR, intraoperative bleeding necessitating volume loading, and elevated systolic RVP immediately after thoracotomy. Conclusion: Short episodes of AF occurred irrespective of the length of oxygen therapy. Occurrence of AF could not be explained by changes in RV function.

Plasma concentrations of brain natriuretic peptide in patients with subarachnoid hemorrhage.

Hyponatremia after subarachnoid hemorrhage (SAH) is commonly associated with diuresis and natriuresis, but the causes are still controversial. We investigated whether brain natriuretic peptide (BNP) was related to such hyponatremia. Plasma BNP concentrations were measured by immunoradiometric assay in 18 patients at 0 to 2 days (period 1), 7 to 9 days (period 2), and > 14 days (period 3) after SAH. Plasma concentrations of antidiuretic hormone (ADH), atrial natriuretic peptide (ANP), and noradrenaline were also measured during period 2. The 11 patients with hyponatremia (serum sodium concentration of < 135 mEq/L) had much higher plasma BNP concentrations during each period than did healthy controls (P < 0.05), whereas the 7 patients with normonatremia did not show statistically higher values. In the patients with hyponatremia, the plasma BNP concentration during period 2 was statistically higher than that during periods 1 and 3 (P < 0.05). The plasma noradrenaline concentration during period 2 was higher in patients with hyponatremia than in those with normonatremia (P < 0.05), whereas the plasma concentrations of ADH and ANP during period 2 were not statistically different between the hyponatremic and normonatremic patients. We conclude that BNP may be related to hyponatremia associated with natriuresis following SAH. The increase of noradrenaline may promote the secretion of BNP.

Atrial natriuretic peptide increases urinary albumin excretion in men with Type 1 diabetes mellitus and established microalbuminuria

Raised plasma concentrations of atrial natriuretic peptide (ANP) have been reported in patients with Type 1 (insulin dependent) diabetes mellitus (DM) who have poor glycaemic control and are associated with the presence of microalbuminuria. To test the hypothesis that elevations in plasma ANP concentration increase urinary albumin excretion in Type 1 DM, we have studied the effects of intravenous infusions of ANP in eight such subjects with established microalbuminuria. Blood glucose was maintained between 4 and 7 mmol l−1 in all subjects for the duration of studies; after euglycaemia had been established, a standard oral water load (20 ml kg−1 plus replacement of urinary losses) was given. Once steady state diuresis was attained, subjects received intravenous infusion of either placebo (0.9 % saline), low dose (2.5 pmol kg−1 min−1) or high dose (5.0 pmol kg−1 kg min−1) ANP solution in a randomized, double-blind protocol. Infusion of ANP caused a dose-dependent increase in urinary albumin excretion rate (placebo, 11.3 (SD 8.9) to 8.7 (SD 6.8) μg min−1; low dose ANP, 12.4 (SD 9.9) to 26.5 (SD 27.5) μg min−1, p < 0.01; high dose ANP 10.3 (SD 7.3) to 36.6 (SD 28.5) μg min−1, p < 0.001, ANOVA). Only high dose ANP caused an increase in urine flow. Blood glucose remained unchanged in all studies. We conclude that intravenous infusions of ANP cause a dose-dependent increase in urinary albumin excretion rate in Type 1 DM subjects with microalbuminuria. These data support the hypothesis that ANP has albuminuric actions which may contribute to microalbuminuria in Type 1 DM. © 1998 John Wiley & Sons, Ltd.

Salt overload does not modify plasma atrial natriuretic peptide or vasopressin during pregnancy in rats.

The present study was carried out to determine whether the increased salt intake induce by increased specific sodium appetite in pregnant rats modifies water-salt homeostasis throughout pregnancy. Two groups of pregnant rats were used, one fed ad libitum with a normal sodium (NS) diet consisting of standard rat chow and distilled water, and the other fed with a high-sodium (HS) diet with free access to chow, distilled water plus saline solution (1.5% NaCl). Virgin rats in dioestrus were also studied as non-pregnant controls. Pregnant animals were studied on days 4, 9, 14, 20 and 21 of gestation at which time body weight, water and saline intake, sodium excretion, plasma atrial natriuretic peptide (ANP) and arginine vasopressin (AVP) concentrations, as well as plasma osmolality were determined. Data showed that water intake was higher in the NS group, but total fluid intake (water plus saline) was higher in the HS group throughout pregnancy. Dietary sodium intake was the same for both groups but total sodium intake (chow plus saline) was 60-98% higher in the HS rats. Pregnant HS rats excreted more fluid (35-50%) and sodium (up to 100%) compared with NS rats, indicating that the animals could change their renal excretion in response to a 2.5-fold higher dietary sodium intake compared with the control level. Salt satiety during pregnancy did not modify plasma ANP concentration. In both groups of pregnant rats ANP levels increased 3-fold on day 14 without significant alteration in sodium excretion, suggesting that the natriuretic action of ANP is attenuated at least after the second week of pregnancy. High sodium intake did not change plasma AVP concentration or osmolality and both groups showed the same gradual decrease in plasma osmolality (approximately 8 mosmol kg-1) at the end of pregnancy that was not accompanied by decreased plasma AVP concentration. The present data show that rats maintain the special homeostatic equilibrium that occurs in normal pregnancy even when they are allowed to increase sodium intake to satisfy their salt appetite during this period of the reproductive cycle.

Beneficial Effect of Atrial Natriuretic Peptide on Pulmonary Gas Exchange in Patients With Acute Lung Injury

The purpose of this study was to investigate the effect of i.v. infusion of atrial natriuretic peptide (ANP) on hemodynamics, pulmonary gas exchange, and urine volume during mechanical ventilation with positive end-expiratory pressure (PEEP) in patients with acute lung injury. Prospective, randomized, comparable study. ICU of a university hospital. Forty patients with moderate acute lung injury (lung injury score > or = 2.0) who required mechanical ventilation with PEEP were studied. The patients were randomly divided into two groups: ANP group (n=20) and control group (n=20). The ANP group received genetic recombination alpha-human ANP (carperitide) at the rate of 0.1 microg/kg/min for 24 h. The control group did not receive ANP. Hemodynamic and blood gas parameters, and urine volume were measured at baseline, 3 h, and 24 h after initiating the ANP infusion. Plasma ANP concentrations markedly (p<0.01) increased from 112.0+/-27.0 to 1,868.3+/-385.3 pg/mL after 24 h in the ANP group, whereas they remained unchanged in the control group. In the ANP group, hemodynamic parameters did not change, but PaO2/FIO2 (fraction of inspired oxygen) and thoracic compliance significantly (p<0.01) increased at 24 h after initiating the ANP infusion, associated with significant (p<0.01) decreases in lung injury score and shunt. Urine volume significantly (p<0.01) increased during 0 to 3 h after initiating the ANP infusion. In the control group, hemodynamics, pulmonary gas exchange, and urine volume did not significantly change during the study period. There were significant differences in PaO2/FIO2 (24 h), thoracic compliance (24 h), lung injury score (24 h), and urine volume (3 h) between the two groups. The results suggest that ANP infusion induces diuresis and improves pulmonary gas exchange in patients with acute lung injury during mechanical ventilation with PEEP.

Mechanism of vasopressin natriuresis in the dog: role of vasopressin receptors and prostaglandins.

Renal effects of physiological amounts of vasopressin were studied in conscious dogs during servocontrolled overhydration (2% body wt). During infusion of vasopressin (50 pg . min-1 . kg body wt-1), plasma vasopressin concentration increased to 2.30 +/- 0.20 pg/ml compared with 0.12 +/- 0.03 pg/ml during control (water diuresis). With vasopressin infusion, urine flow was significantly lower (0.30 +/- 0.10 ml/min) and sodium excretion (UNaV) was significantly higher (58.0 +/- 15.8 micromol/min) than without vasopressin (4.6 +/- 0.4 ml/min and 14.4 +/- 4.1 micromol/min, respectively). Deamino-[Cys1,D-Arg8]vasopressin, a V2 receptor agonist (4 pg . min-1 . kg-1), mimicked the antidiuretic response (0.20 +/- 0.03 ml/min) without changing UNaV (9.7 +/- 4.4 micromol/min). Indomethacin given during arginine vasopressin (AVP) infusion suppressed prostaglandin E2 excretion, intensified the antidiuresis (0.10 +/- 0.02 ml/min), and abolished the natriuresis (13.4 +/- 3.7 micromol/min). During AVP infusion, UNaV was highly correlated (r = 0.85) with prostaglandin E2 excretion. Blood pressure, glomerular filtration rate, plasma atrial natriuretic peptide concentration, and the rate of proximal tubule reabsorption (derived from lithium clearance) were similar in all series. The data indicate that, in the dog, physiological amounts of vasopressin can induce natriuresis, probably through activation of non-V2 receptors and the intrarenal synthesis of prostaglandins.

Twin-to-Twin Transfusion Syndrome: Polyhydramnios-Associated Changes in Maternal Plasma Volume and Maternal Plasma Aldosterone Concentrations

Objective: Our aim was to evaluate the consequences of polyhydramnios on maternal plasma volume and maternal serum aldosterone and atrial natriuretic peptide (ANP) concentrations in monochorionic twin pregnancies complicated by twin-to-twin transfusion syndrome (TTTS). Methods: The maternal plasma volume, ionograms as well as plasma ANP and aldosterone concentrations were compared in normal monochorionic diamniotic twin pregnancies and in TTTS. Results: The maternal plasma volume was normal in TTTS despite severe polyhydramnios. The plasma aldosterone concentration was higher in pregnancies complicated by TTTS. Conclusion: The high plasma aldosterone concentration is likely to maintain normal plasma volume despite progressive extravascular volume enhancement. This suggests that TTTS is present early in pregnancy as a chronic phenomenon starting before its clinical expression and may trigger compensatory maternal hyperaldosteronism.

Antidiuretic Effect of Eel ANP Infused at Physiological Doses in Conscious, Seawater-Adapted Eels, Anguilla japonica

Atrial natriuretic peptide (ANP) is known as a potent natriuretic/diuretic hormone in vertebrates. However, eel ANP infused at doses that did not alter arterial blood pressure (0.3-3.0 pmol/kg/min) decreased urine volume and increased urinary Na concentration in seawater (SW)-adapted eels but not in freshwater (FW)-adapted eels. The renal effects were dose-dependent and disappeared after infusate was switched back to a vehicle (0.9% NaCl). Urinary Na excretion (volume x Na concentration) did not change during ANP infusion. ANP infusion increased plasma ANP concentration, but the increase at the highest dose was still within those observed endogenously after injection of hypertonic saline. Urinary Mg and Ca concentrations increased during ANP infusion in SW eels, but urinary Ca excretion decreased in FW eels. Plasma Na concentration profoundly decreased during ANP infusion only in SW eels, suggesting that ANP stimulates Na extrusion via non-renal routes. These results indicate that ANP is a hormone which specifically extrudes Na ions and thereby promotes SW adaptation in the eel. This is in sharp contrast with mammals where ANP is a volume regulating hormone that extrudes both Na and water.

Streptozotocin-induced diabetes has differential effects on atrial natriuretic peptide synthesis in the rat atrium and ventricle: a study by solution-hybridization-RNase protection assay

In rats with streptozotocin (STZ)-diabetes for 2 or 4 weeks, the atrial natriuretic peptide (ANP) concentrations in the atria decreased whilst that of ANP in the plasma and ventricles increased. ANP concentrations in the hypothalamus and in the brainstem did not change in either 2- or 4-week diabetic rats. Atrial ANP content was partly restored by insulin replacement in 4-week diabetic rats. Plasma ANP concentrations and ventricular ANP contents were reversed to normal by insulin treatment in both 2- and 4-week diabetic rats. Solution-hybridization-RNase protection assay showed a significant increase in the preproANP mRNA expression in the ventricles but not in the atria. These results indicated that the STZ-diabetes increased the synthesis of ANP in the ventricles and consequently its release from the ventricles. The synthesis of ANP in the atria did not change as judged from the preproANP mRNA expression but the release of ANP from the atria might also be increased for ANP content decreased in the atria. The reason for the difference in the response of atrial and ventricular preproANP concentrations to STZ-diabetes is not known.

Fluid administration attenuates the haemodynamic effect of frusemide in running horses.

The effect of blood volume repletion after frusemide administration on the right atrial and pulmonary artery pressure responses of horses to exercise has not been reported. We examined right atrial and pulmonary artery pressure and plasma atrial natriuretic peptide concentration (ANP) responses to an incremental exercise test in 6 Standardbred mares. Horses were treated, in a 3 way cross over design, with isotonic saline, frusemide (1 mg/kg bwt, i.v.), and frusemide followed 3 h later by lactated Ringer's solution (12 ml/kg bwt, i.v.). Three and a half hours after saline or frusemide administration the horses completed a standard exercise test. Frusemide significantly affected the right atrial and pulmonary artery pressure and ANP responses to exercise. Fluid administration decreased plasma total protein concentrations at rest and during running and abolished the effects of frusemide on the haemodynamic and ANP responses to exercise. These results suggest that the haemodynamic effect of frusemide in running horses is mediated, in large part, by a reduction in plasma and blood volume.

Atrial natriuretic peptide and arginine-vasopressin secretion in patients with active renal stone disease.

The pathogenesis of active renal stone disease (ARSD) is still not fully elucidated. In the present study the role of atrial natriuretic peptide (ANP) and arginine-vasopressin (AVP) as potential pathogenetic factors in ARSD were examined. Thirty patients with ARSD and 21 healthy subjects (HS) were examined both under bed rest (BR) and head-out water immersion (WI) conditions. Serum concentrations of electrolytes (Na, Ca, Mg), ANP and AVP were assessed before (0'), and after 60 and 120 minutes of BR or WI, respectively. Urinary excretions of Na, Ca, Mg, and oxalates were also estimated during BR and WI. Patients with ARSD showed higher basal plasma levels of ANP and a greater response of ANP secretion, but a lower suppression of plasma AVP to WI induced hypervolaemia as compared with the controls. In addition, in patients with ARSD the physiological relationship between plasma AVP concentration and urinary excretion of Ca and Mg (positive correlation), between plasma ANP level and urinary excretion of Ca and Mg (negative correlation), and between plasma ANP and AVP concentration (negative correlation), respectively, were absent. In addition, patients with ARSD showed a positive correlation between plasma ANP and urinary oxalate excretion. From the results obtained in this study we conclude that both AVP and ANP may be involved in the pathogenesis of ARSD.