Plasma Atrial Natriuretic Peptide Concentrations Research Articles

Receptors for atrial natriuretic peptide are decreased in the kidney of rats with streptozotocin-induced diabetes mellitus.

To determine whether decreased renal responsiveness to atrial natriuretic peptide (ANP) in diabetes is mediated by alterations in the renal ANP receptor, ANP receptor density and affinity were measured 17-20 d after streptozotocin injection and compared with values in vehicle-treated controls and streptozotocin-treated rats made euglycemic with insulin. Plasma ANP concentration was significantly greater in hyperglycemic diabetic rats than in control or euglycemic diabetic rats. Both in glomeruli and inner medulla, ANP receptor dissociation constant did not differ among the three study groups, whereas the maximum binding capacity was decreased significantly in hyperglycemic diabetics in comparison with controls and euglycemic diabetics. Glomerular clearance receptors were also decreased significantly in hyperglycemic diabetic rats in comparison with control and euglycemic diabetic rats. To determine whether the decreased number of renal ANP receptors in diabetic rats was associated with a decreased biological response, we measured ANP-dependent cyclic GMP (cGMP) accumulation by isolated glomeruli and inner medullary collecting duct cells in vitro. cGMP accumulation was significantly less in hyperglycemic diabetic rats than in controls or euglycemic diabetic rats both in the presence or absence of the phosphodiesterase inhibitor zaprinast. cGMP phosphodiesterase activity in inner medullary collecting duct cells obtained from control and hyperglycemic diabetic rats did not differ. Thus, the decreased number of biologically active ANP receptors in the kidneys of diabetic rats is accompanied by decreased biological responsiveness in vitro and provides a potential explanation for the reduction in renal sensitivity to ANP in this condition.

The effect of β1-blocker bisoprolol on atrial natriuretic peptide plasma levels in hypertensive patients

The aim of this study was to evaluate the effects of the high selective β1-blocker bisoprolol on atrial natriuretic peptide (ANP) plasma levels in patients with a moderate essential hypertension. The study was divided into two parts: a long-term and a short-term one. In part 1, the long-term effects of the drug, given orally at a daily dose of 10 mg, on plasma ANP concentrations were studied in correlation with the blood pressure and the echocardiographic dimensions of the left heart cavities in the lying position. Plasma ANP levels were raised by 20% despite the drop in blood pressure and the very small, but statistically significant, decrease in left atrial and ventricular diameters. In part 2, the acute effects of a single oral dose of 20 mg bisoprolol in relation to postural changes were studied. Plasma ANP levels in the sitting position were lower than in when lying down, but in both positions they were slightly higher after betablockers. The above findings, taken together with the literature data, favor the theory that the antihypertensive action of beta adrenergic blockers is partially due to the increased secretion of ANP.

Responses of plasma concentrations of A type natriuretic peptide and B type natriuretic to alacepril, an angiotensin-converting enzyme inhibitor, in patients with congestive heart failure.

BACKGROUND--Plasma concentrations of A type or atrial natriuretic peptide (ANP) and B type or brain natriuretic peptide (BNP) are increased in patients with congestive heart failure (CHF). OBJECTIVE--To examine the haemodynamic and hormonal responses, especially of ANP and BNP, to oral administration of an angiotensin-converting enzyme (ACE) inhibitor in patients with CHF and in controls. PATIENTS--12 patients with CHF and 11 controls. METHODS--Haemodynamic variables and plasma concentrations of ANP, BNP, and other hormones were serially measured for 24 hours after alacepril (37.5 mg) was given by mouth. RESULTS--Pulmonary capillary wedge pressure and systemic vascular resistance decreased significantly in both groups. The cardiac index increased only in the CHF group. In patients with CHF pulmonary capillary wedge pressure, systemic vascular resistance, and cardiac index were significantly changed from 1 to 12 hours after alacepril administration. Plasma ANP and BNP decreased significantly after alacepril was given to the CHF group: neither concentration changed in the control group. In the CHF group plasma ANP was significantly lower between 1 and 6 hours and was highly significantly correlated with pulmonary capillary wedge pressure. Plasma BNP, however, was significantly lower between 6 and 24 hours after alacepril and was not correlated with pulmonary capillary wedge pressure. CONCLUSIONS--The response of plasma BNP after alacepril administration occurred later and lasted longer than the plasma ANP response. This may indicate that the mechanisms of synthesis, secretion, or degradation of the two peptides are different.

How does intermittent pacing modify the response to rapid ventricular pacing in experimental heart failure?

Rapid ventricular pacing is widely accepted as a useful model to produce heart failure. The heart failure is associated with reduced myocardial energy stores and absence of cardiac hypertrophy. In this study, it was hypothesized that a modification of the protocol to intermittent pacing would permit time for partial recovery of myocardial energetics leading to improved cardiac function and development of hypertrophy. Eight dogs underwent conventional continuous right ventricular pacing to a biologic endpoint of severe heart failure (group 1). Another eight dogs underwent an intermittent pacing protocol over 7 weeks, consisting of 48-hour pacing alternating with 24-hour sinus rhythm (group 2) so as to produce the same total exposure to continuous pacing as in group 1. Six additional normal dogs were used as control animals for tissue metabolic data. Although both paced groups had similar directional changes in hemodynamic, neurohormonal, and echocardiographic variables, the absolute increases in pulmonary capillary wedge and right atrial pressures in group 2 (13 ± 8 and 3 ± 4 mmHg, respectively) were less marked than in group 1 (29 ± 5 and 12 ± 4 mmHg, respectively; both P = .002). Group 2 also had a more modest rise in plasma atrial natriuretic peptide and norepinephrine concentrations. There was no significant increase, however, in left ventricular mass in either group, and myocardial adenosine 5′-triphosphate levels were reduced to a similar extent compared to the control animals. Intermittent pacing produces a less advanced syndrome of heart failure than continuous pacing. Furthermore, the data suggest that reduced energy stores are not the predominant mechanism for impaired cardiac function, although they may contribute to the failure to hypertrophy in this model.

Effects of acute hyperinsulinemia on plasma atrial and brain natriuretic peptide concentrations

Impaired renal sodium excretion and increased plasma atrial natriuretic peptide (ANP) levels have been reported in patients with hypertension associated with insulin resistance and hyperinsulinemia. To clarify the interrelationship between hyperinsulinemia and plasma natriuretic peptides, we investigated the effects of physiological and non-physiological hyperinsulinemia on the plasma ANP and brain natriuretic peptide (BNP) levels. Plasma immunoreactive insulin (IRI), ANP and BNP levels were determined by a euglycemic-hyperinsulinemic glucose clamp in 20 patients with non-insulin-dependent diabetes mellitus, by a glucose challenge test in 22 normal subjects and by an insulin challenge test in six normal subjects. Both in the glucose clamp and the glucose challenge test, plasma ANP showed a significant increase in association with increased plasma IRI and plasma volume. However, there was no significant correlation between the changes in plasma ANP levels and plasma IRI levels in view of the peak values and the area under the curve of their responses. In addition, the plasma ANP did not show any significant change despite the marked elevation of plasma IRI in the insulin challenge test. There was no significant change in plasma BNP under any of the hyperinsulinemic conditions. These findings provide in vivo evidence for the lack of a direct effect of acute hyperinsulinemia on natriuretic peptides, although the chronic effects of hyperinsulinemia remain to be elucidated.

Beneficial clinical effect of very early enalapril treatment in patients with acute left ventricular failure complicating myocardial infarction

Acute myocardial infarction (AMI) leads to left ventricular dysfunction, the extent of which predicts mortality. We studied the effect of very early enalapril treatment in patients with left ventricular failure (Killip classification II-III) resulting from AMI. In a double-blind randomized trial, patients on conventional treatment were started on placebo (PL, n = 15) or 2.5 mg enalapril (EN, n = 15) twice daily as early as 24 to 30 h after AMI and were followed up over a period of 21 days. One patient died in each treatment group. There were three dropouts in the placebo group (progressive heart failure requiring antiotensin-converting enzyme inhibition) and one dropout in the enalapril group (malignant ventricular arrhythmias). Plasma atrial natriuretic peptide (ANP) and norepinephrine decreased similarly in both groups from elevated baseline concentrations. The patients with the highest baseline ANP levels died in both groups: EN: 579 fmol/ml (mean 65.3 +/- 34.4 fmol/ml), PL: 403 fmol/ml (mean 63.5 +/- 37.6 fmol/ml). Killip classification improved in 9 of 13 patients on enalapril but only in 5 of 11 patients on placebo. On echocardiography an increase in fractional shortening (FS) (3.2 +/- 7.5%, p < 0.05) was found with enalapril only. Patients on placebo required more diuretics, and plasma aldosterone increased threefold. Thus, very early enalapril treatment may help prevent left ventricular failure after AMI. Extremely high initial plasma ANP concentrations may predict an unfavorable outcome.

Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist.

The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.

Neuroendocrine control of blood volume, blood pressure and cardiovascular function in horses

SummarySeveral body systems make critical contributions to the defence of blood volume, mean arterial pressure and plasma tonicity. These mechanisms ensure adequate blood flow to the working muscles and vital tissues along with the provision of adequate fluid volume for sweating and thermoregulation. The present paper integrates data from several recent studies that examined the neuroendocrine control of cardiovascular function in exercising horses. These studies focused on the effects of exercise on plasma concentrations of atrial natriuretic peptide (ANP), arginine vasopressin (AVP), plasma renin activity (PRA) and aldosterone (ALDO), hormones associated with the regulation of blood pressure, the distribution of blood flow and the long term control of vascular fluid volume. Data were collected during incremental and endurance exercise, following frusemide administration and after splenectomy. Increases in ANP during exercise were associated with increased atrial pressure and stretching of the atrium. Increases in PRA and ALDO are correlated with increases in sympathetic activity during incremental exercise and with decreases in plasma Na+ and CI− concentrations. Plasma AVP increases later in exercise in response to fluid losses, increases in plasma osmolality, and decreases in right atrial pressure. AVP has a minimal effect on renal function during exercise and may be more important during recovery, when it stimulates thirst and drinking. Frusemide and splenectomy decrease atrial pressure, resulting in lower plasma ANP and greater plasma AVP concentrations during steady‐state submaximal exercise. The ANP and AVP responses are part of the neuroendocrine action of the cardiopulmonary baroreflex which appears to mediate the accommodation of the mobilised splenic reserve in the horse. In summary, exercise induced increases in ANP, AVP, PRA and ALDO in the horse appear to play an important role in cardiovascular homeostasis.

Effects of phenylephrine induced increase in arterial pressure and closure of the ductus arteriosus on the secretion of atrial natriuretic peptide (ANP) and renin in the ovine fetus

Although atrial natriuretic peptide (ANP) has been detected in the plasma of late gestation fetal sheep, stimuli that control its secretion and its function in regulating fluid volume are unclear. To determine stimuli that increase ANP secretion and to ascertain whether the response is a function of gestation we studied 20 chronically cannulated fetal sheep. The fetuses were divided into 3 groups; Group I (age range 118–129 days), Group II (age range 129–141 days) and Group III (age range 127–137 days) gestation. Arterial pressure was increased to within a physiologic range by infusing phenylephrine at 6 μg/min at 0.1 ml/min into the inferior vena cava of the fetus (Groups I and II). Corrected for body weight fetuses in Group I received 2 μg/kg/min whereas fetuses in Group II received 1.66 μg/kg/min. In the fetuses in Group III preload to the right side of the heart was increased by inflating an occluder cuff was placed around the ductus arteriosus. Systemic mean arterial pressure (MAP) increased significantly in fetuses in Groups I and II. Plasma ANP concentrations increased significantly in all fetuses. Plasma Renin Activity (PRA) decreased significantly in the fetuses in Group II. These results suggest that phenylephrine infusion and closure of the ductus arteriosus in utero increase circulating ANP in fetal sheep.

Relationship between left atrial pressure and atrial natriuretic peptide in children with cardiac disease.

To evaluate the relationship between atrial pressure and the concentrations of atrial natriuretic peptide (ANP) in plasma of children with cardiac disease combined with increased left atrial loading. We extracted plasma ANP through a Sep-Pak C18 cartridge and proceeded to radioimmunoassay. Of the nine children, aged from 20 days to 10 years, cardiac diseases included transposition of the great arteries (four cases), ventricular septal defect (three cases), patent ductus arteriosus (one case) and mitral regurgitation (one case). The concentrations of ANP in plasma in the left atrium were greater than in the inferior vena cava, and the concentrations of ANP in plasma in the inferior vena cava correlated significantly with the mean left atrial pressure (r = 0.89, p < 0.01), and the concentrations of ANP in plasma in the left atrium correlated significantly with the mean left atrial pressure (r = 0.85, p < 0.01). This study indicated that left atrial pressure may have an important influence on secretion of ANP in various cardiac conditions.

Participation of endogenous atrial natriuretic peptide in the regulation of urinary protein excretion in experimental diabetic rats.

1. In order to determine whether atrial natriuretic peptide might play a role in the development of glomerular hyperfiltration in diabetes mellitus, we examined the effects of administration of glucose, albumin, atrial natriuretic peptide and an atrial natriuretic peptide receptor antagonist on renal function in rats with streptozotocin-induced diabetes mellitus and vehicle-treated control rats. 2. Four weeks after treatment, rats with diabetes mellitus had a higher mean plasma atrial natriuretic peptide concentration than controls [152 +/- 5 (SE) versus 115 +/- 6 pg/ml, P < 0.01] and a higher glomerular filtration rate (3.3 +/- 0.1 versus 2.7 +/- 0.2 ml min-1 kg-1, P < 0.05). 3. Infusion of albumin or glucose caused significant increases in atrial pressure, plasma atrial natriuretic peptide concentration and urinary excretion of sodium and protein in both groups of rats. 4. Increasing plasma atrial natriuretic peptide concentration by 60% via atrial natriuretic peptide infusion increased urinary excretion of sodium and protein in both control rats and rats with diabetic mellitus. 5. Administration of the atrial natriuretic peptide receptor antagonist HS-142-1 to diabetic rats resulted in diminished urinary excretion of both sodium (-61 +/- 14%, P < 0.02) and protein (-51 +/- 17%, P < 0.05). These changes were associated with a significant reduction in glomerular filtration rate (-32 +/- 11%, P < 0.05) and urinary cGMP excretion (-40 +/- 14%, P < 0.05). No significant effects of HS-42-1 on renal function were observed in control rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Prevention of glomerular hyperfiltration in rats with streptozotocin-induced diabetes by an atrial natriuretic peptide receptor antagonist

The contribution of atrial natriuretic peptide (ANP) to the development of glomerular hyperfiltration in diabetes was investigated by examining the effects of HS-142-1, a non-peptide antagonist of biological receptors for ANP, on glomerular filtration rate (GFR) and renal plasma flow (RPF) in rats with streptozotocin-induced diabetes. Three to four weeks after streptozotocin injection, the plasma concentration of ANP, urinary cyclic GMP excretion rate, GFR, and RPF were significantly higher in diabetic rats than in control rats. The increase in GFR and RPF in diabetic rats was significantly reduced, in a dose-dependent manner, by a single intravenous injection of HS-142-1; the maximal effect was apparent at a dose of 10 mg per kg of body weight. Continuous subcutaneous administration of HS-142-1 with an osmotic minipump for 3 to 4 weeks, beginning 2 days after streptozotocin injection, prevented the increases in urinary cyclic GMP excretion rate, GFR, and RPF observed in untreated diabetic rats. These results highlight the importance of ANP in the development of diabetic glomerular hyperfiltration and indicate that this condition can be prevented by continuous inhibition of the action of ANP.

The Effects of Posture Change and Continuous Positive Airway Pressure on Cardiac Natriuretic Peptides in Congestive Heart Failure

We studied changes in the peripheral plasma levels of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) in seven patients with congestive heart failure (CHF) during four 1-h protocols during which patients maintained either an upright or a supine posture with or without nasal continuous positive airway pressure therapy (N-CPAP) at a pressure of 10 cm H2O (FIO2 = 0.21). The mean plasma ANP concentration of patients increased significantly from baseline at the end of 1 h of recumbency (65.9 +/- 5.8 to 82.6 +/- 8.3 pg/mL (mean +/- standard error); p < 0.05). This increase was prevented by concomitant N-CPAP therapy (72.1 +/- 8.0 to 61.0 +/- 8.8 pg/mL; p = NS). The mean level of ANP decreased significantly (71.9 +/- 9.0 to 62.5 +/- 8.0 pg/mL; p < 0.05) while patients simply maintained an upright posture. A significant reduction was also observed when patients remained upright with accompanying N-CPAP (72.6 +/- 10.9 to 54.6 +/- 4.3 pg/mL; p < 0.05). There were no significant changes observed in the mean level of BNP for any of the protocols undertaken. We conclude that in patients with chronic CHF, (1) an increase in ANP concentration occurs with recumbency, and this can be prevented by N-CPAP therapy; (2) a decrease in ANP occurs with maintenance of an upright posture, and that this reduction may be augmented by N-CPAP; and (3) no net change in BNP concentration occurs with either posture change or N-CPAP.

Dietary Sodium Modulates Neonatal but Not Adult Cardiac Atrial Natriuretic Peptide in Rats

After an initial postnatal diuresis, neonates are in positive sodium balance. Because atrial natriuretic peptide (ANP) contributes to sodium homeostasis, this study was designed to evaluate the maturational effects of increased dietary sodium intake on cardiac ANP production. Preweaned Sprague-Dawley rat pups were artificially reared by feeding them either a normal-sodium or high-sodium diet for 7 d and were compared with maternally reared rat pups. Adult rats were divided into three groups: the first group was given ad libitum rat food and 1% sodium chloride to drink, the second group was pair-fed with this group but given tap water to drink, and the third group was fed ad libitum rat food and water for 10 d. Atrial and ventricular pro-ANP and ANP contents and plasma ANP concentrations were measured by RIA. Steady state atrial and ventricular ANP mRNA expression was determined by Northern and dot-blot analysis. There was a 2-fold increase in atrial pro-ANP and ANP content and a 50% decrease in plasma ANP concentration in preweaned rat pups fed a high-salt diet. In contrast, atrial pro-ANP and ANP content and plasma ANP concentration were not affected by increased sodium intake in adult rats. Atrial and ventricular ANP mRNA levels and ventricular pro-ANP and ANP contents were not altered by dietary sodium at either age. We conclude that chronic increase in sodium intake in the preweaning period results in increased storage of atrial pro-ANP. The decrease in plasma ANP concentration in these preweaned rats may be due to reduced basal secretion or enhanced degradation of the peptide.

Renal, endocrine and vascular effects of atrial natriuretic peptide in a novel vasopressin‐deficient genetically hypertensive strain of rat

In the absence of the potentially confounding influence of vasopressin in hypertension, the effects of atrial natriuretic peptide (ANP) on arterial blood pressure and renal handling of water and sodium were assessed from comparison of responses to intravenous ANP infusion in anaesthetized vasopressin-deficient New Zealand genetically hypertensive (DI/H) rats and their normotensive substrain (DI/N). After 320 min of hypotonic saline infusion, plasma ANP concentration was significantly higher in DI/H compared with DI/N rats. ANP administration increased circulating ANP concentration in both groups. Plasma angiotensin II concentration was higher in DI/H than in DI/N rats; infusion of ANP raised circulating angiotensin II in both groups though this achieved statistical significance only in DI/N rats. Plasma aldosterone concentrations were initially similar in normotensive and hypertensive animals and, in both, were reduced markedly by I.V. ANP infusion. Administration of ANP produced sustained hypotension in both groups. However, the hypotensive effect of ANP was more pronounced in DI/H compared with DI/N rats. Heart rate was initially similar in the two groups, and infusion of ANP produced no detectable change. By comparison with animals maintained on hormone-free infusate, urine flow increased markedly over the 80 min period of ANP infusion in both groups, by 142% in DI/H rats and 127% in DI/N rats. ANP administration produced a natriuresis in both groups but the increase in Na+ excretion was much greater in DI/H (342%) than in DI/N (139%) rats. It appears from the current study that vasopressin-deficient hypertensive rats are more sensitive to ANP with regard to effects on blood pressure and renal excretion than their vasopressin-deficient normotensive substrain. These differences may, in part, reflect adjustments to long-term elevation in blood pressure and in plasma ANP concentration in hypertension and, in part, rely on the associated disturbances in related endocrine systems.

Atrial natriuretic peptide ANP(1–98) and ANP(99–126) in patients with severe chronic congestive heart failure: Relation to echocardiographic measurements

Studies in patients with moderate heart failure have shown a positive relation between atrial size and plasma atrial natriuretic peptide (ANP)(99–126) concentrations; however, the relation of the hormone level and left atrial size and left ventricular function in patients with severe chronic heart failure has not been determined. Fifty-three patients from the Cooperative North Scandinavian Enalapril Survival Study with severe chronic heart failure were evaluated with M-mode echocardiography and determination of plasma concentrations of ANP(99–126). In 35 patients, the plasma level of N-terminal ANP(1–98) was also measured. A significant negative relation was found between ANP(1–98), ANP(99–126), and left atrial diameter ( r = −.28, P = .05 and r = −.41, P < .005, respectively). Plasma concentrations of both ANP(1–98) and ANP (99–126) were related to left ventricular systolic function as determined by the systolic time interval index ( r = .4, P < .05 and r = .29, P < .05, respectively). A significant improvement of left ventricular systolic function was found in the enalapril group but not in the placebo group. After 6 weeks of therapy, no correlation was found between changes in left atrial size or systolic function or changes in either the ANP(1–98) or ANP(99–126) concentration. The results indicate that high ANP(1–98) or ANP(99–126) plasma concentration is determined by the depressed left ventricular function rather than increased left atrial size in patients with chronic severe heart failure. The findings suggest that the ANP release relation to atrial pressure/atrial size is distorted in severe heart failure.

Elevated Plasma Atrial Natriuretic Peptide Concentrations in Hypertensive Patients with Acute Myocardial Infarction

Atrial natriuretic peptide (ANP) has been extensively studied in cardiovascular disorders in recent years. Particular attention has been paid to the role of ANP in the pathogenesis of hypertension and congestive heart failure and in the neurohormonal response to myocardial infarction. However, no published data are available on the significance of ANP in hypertensive patients with acute myocardial infarction. We studied the relationship between plasma ANP concentration and systolic blood pressure, diastolic blood pressure, left atrial dimension, left ventricular diastolic dimension and left ventricular mass index in patients with essential hypertension in the acute phase of myocardial infarction. Plasma ANP concentrations were determined at 0, 4, 8, 16, 24, 48 and 72 h after admission in 40 patients with a first myocardial infarction (18 hypertensive patients, group 1; 22 normotensive patients, group 2). Left atrial dimension and left ventricular diastolic dimension were assessed echocardiographically within the first 48 h of acute myocardial infarction. Maximum and mean plasma ANP values at 0, 4, 8, 16, 24, 48, and 72 h as well as mean ANP concentrations within the 72 h period were higher in group 1 than in group 2 (P < 0.001). Plasma ANP concentration, left atrial dimension (r = 0.59) and left ventricular diastolic dimension (r = 0.56) were positively correlated in both groups. Acute myocardial infarction is characterized by a more pronounced rise in plasma ANP concentration in hypertensive patients than in those without a history of hypertension. Plasma ANP concentration correlates with left heart chamber sizes.

Elevated plasma atrial natriuretic peptide concentrations in hypertensive patients with acute myocardial infarction

Elevated plasma atrial natriuretic peptide concentrations in hypertensive patients with acute myocardial infarction

757-5 Hemodynamic Effects of Synthetic Human Brain Natriuretic Peptide Infusion in Patients with Severe Congestive Heart Failure: A Placebo-controlled, Crossover Trial

Brain natriuretic peptide IBNP) and atrial natriuretic peptide (ANP) are naturally-occurring peptide hormones with vasodilating and natriuretic properties, Although the two peptides are structurally similar, the primary site of synthesis, receptor binding properties and metabolic clearance pathways of BNP are distinct from those of AN P. While the plasma concentrations of both BNP and ANP are increased in patients with congestive heart failure (CHF), the biologic significance of this increase is uncertain since the vasodilatory effects of exogenous ANP are attenuated in patients with CHF. To determine if the vasodilating effects of BNP are similarly attenuated in patients with CHF, the acute hemodynamic effects of exogenous synthetic human BNP infusion (Scios Nova) were determined in 10 patients with chronic NYHA Class III congestive heart failure (mean age 55 yrs, mean LVEF 21%) in a doubleblind, placebo-controlled crossover trial. BNP or matching placebo solutions were administered intravenously in 4 incremental doses ranging 0.003-0.1 JLg!kgfmin over 6 hours on two consecutive days. Heart rate (HR). mean arterial pressure (MAP). mean pulmonary artery pressure (PAP). pulmonary capillary wedge pressure (PCWP) and cardiac index (CI) were measured before study drug administration on each day and 60 and 90 minutes after each upward dose increment. Hemodynamic measurements before drug administration and peak hemodynamic responses to administration of human BNP and placebo were as follows: HR MAP PAP PCWP CI Before Placebo 72 ± 9 81 ± 8 36 ± 8 23 ± 5 2.3 ± 0.3 Peak Placebo 83 ± 12 75 ± 7 35 ± 8 21 ± 6 23 ± 0.3 Before BNP 72 ± 11 85 ± 10 38 ± 7 25 ± 5 2.1 ± 0.3 Peak BNP 88 ± 20 68 ± 9 * 22 ± 7 * 10 ± 5 * 2,7 ± 0.5 † * indicates p &lt; 0.01 versus peak placebo † indicates p = 0.055 versus peak placebo Two patients did not tolerate the highest dose of BNP because of transient symptomatic hypotension. In conclusion, short-term intravenous infusion of human BNP acutely improves hemodynamic function in patients with advanced CHF. These findings contrast with previous studies demonstrating attenuated acute hemodynamic effects of exogenous ANP and suggest that the physiologic and pharmacologic roles of these two natriuretic peptide hormones may differ.

Impaired response of atrial natriuretic peptide to acute water load in obesity and in anorexia nervosa

Plasma atrial natriuretic peptide (ANP) concentrations were determined in basal conditions and after infusion of 1000 ml of 0.9% NaCl in women with anorexia nervosa, in normotensive obese women and in healthy women of the control group. Additionally, in the obese women and in the controls, plasma ANP was measured after iv injection of clonidine. Anorectic patients were investigated in the period of weight loss (mean deficit of body weight was 40%). The mean body mass index (BMI) in the obese women was 36.44 +/- 0.36 kg/m2. Basal plasma ANP concentrations were significantly higher in both anorectic and obese women (p < 0.001 and p < 0.01, respectively). The response of ANP to acute water load was markedly blunted in anorexia nervosa and in obesity (delta % = 232% in control group, 14% in anorexia nervosa and 21% in obesity. A significant increase of ANP was found after iv injection of clonidine in the control group and in obesity (p < 0.001 and p < 0.01, respectively). However, the increase of response (expressed as a percentage change) in obese patients was lower than that in the control group (delta % = 64% and 199%, respectively). The response of ANP to alpha 2-adrenergic stimulation was higher than to hemodynamic stimulus. Our results suggest that the disturbed control of neuropeptides and neurotransmitters as well as changes in peripheral metabolism may explain the impaired responsibility of ANP to hemodynamic stimuli in anorectic and obese patients.