Attenuated forearm vasodilative response to intra-arterial atrial natriuretic peptide in patients with heart failure

It has been shown that renal responses to atrial natriuretic peptide (ANP) are markedly attenuated in patients with heart failure. This study aimed to determine if vasodilative response to ANP is altered in patients with heart failure. In patients with heart failure (n = 7) and age-matched normal subjects (n = 7), forearm blood flow was measured using a strain-gauge plethysmograph during intra-arterial infusion of alpha-human ANP (50, 100, 200, and 400 ng/min) or nitroglycerin (100, 200, 400, and 600 ng/min). Forearm vasodilatation evoked with intra-arterial alpha-human ANP in patients with heart failure was considerably less (p less than 0.01) than that in normal subjects. In contrast, nitroglycerin produced comparable forearm vasodilatation in the two groups. Plasma ANP and cyclic guanosine monophosphate (GMP) levels at rest were higher in patients with heart failure than in normal subjects (p less than 0.05 for both), but the increases in plasma ANP and cyclic GMP in the venous effluents during intra-arterial ANP infusion did not differ between the two groups. These results indicate that the direct vasodilative effect of ANP on forearm vessels was attenuated in patients with heart failure as compared with that in normal subjects. The mechanisms responsible for this alteration are not clear but might involve mechanisms other than down-regulation of the ANP receptors because the increases in venous plasma cyclic GMP caused by intra-arterial ANP were comparable between patients with heart failure and normal subjects.     

Plasma alpha-human atrial natriuretic peptide concentration in patients with acute lung injury.

To elucidate the pathophysiologic role of alpha-human atrial natriuretic peptide (alpha-hANP) in acute lung injury, plasma alpha-hANP concentrations were measured in 15 patients with severe lung injury, and the relationships of plasma alpha-hANP levels to the severity of lung injury, diuresis/natriuresis, and fluid balance were examined. The mean concentrations of plasma alpha-hANP (188.0 +/- 94.6 pg/ml) in patients with severe lung injury at the entry into the study were significantly (p less than 0.001) higher than those in normal subjects (31.7 +/- 12.0 pg/ml). Plasma alpha-hANP levels decreased in parallel with the improvement of lung injury in nine of 15 patients, whereas they changed little, if any, in the patients who did not recover. Plasma alpha-hANP concentrations correlated positively with urine volume, urinary sodium excretion, and excreted fraction of filtered sodium, but they correlated negatively with fluid balance at the onset of the disease as well as during the clinical course. It is suggested that elevation of circulatory alpha-hANP may reflect an adaptative mechanism to remove excessive fluid retention and reduce pulmonary hypertension for acute lung injury.     

Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure.

In non-cirrhotic patients, splanchnic, renal and pulmonary vascular beds are involved in the plasma clearance for atrial natriuretic peptide (ANP). In patients with cirrhosis, endogenous plasma ANP clearance by these vascular beds has not been systematically studied. In addition, the influence of the severity of liver failure on plasma ANP clearance is not known. Thus, in this study we determined plasma ANP clearance by splanchnic, renal and pulmonary circulations using both arteriovenous differences in plasma ANP concentrations and organ plasma flow in 11 patients with cirrhosis. The role of forearm circulation in plasma ANP extraction was also studied. Splanchnic plasma ANP extraction was 29 +/- 7% (mean +/- S.E.) and splanchnic plasma ANP clearance was 404 +/- 130 ml/min (n = 7). Renal plasma ANP extraction and clearance were 32 +/- 8% and 191 +/- 57 ml/min, respectively. Forearm plasma ANP extraction was 11 +/- 4%. Pulmonary plasma ANP extraction and clearance were 8 +/- 5% and 312 +/- 272 ml/min, respectively. A significant negative correlation was found between logarithm of serum bilirubin concentration, on one hand, and splanchnic and forearm plasma ANP extraction, on the other. A significant negative correlation was found between Pugh's score, on one hand, and renal plasma ANP extraction and clearance, on the other. No significant correlation was found between the severity of liver failure and pulmonary plasma ANP extraction and clearance. As a result, we conclude that in cirrhotic patients splanchnic, renal, forearm and pulmonary vascular beds are involved in plasma ANP extraction and clearance. Plasma ANP extraction and/or clearance may be attenuated in the splanchnic, renal and forearm circulations due to liver failure.     

Plasma levels of atrial natriuretic peptide in patients with chronic renal failure

Plasma levels of atrial natriuretic peptide (ANP) were measured in 57 patients with chronic renal failure (CRF) using a specific and sensitive RIA. The mean plasma ANP level in CRF patients [173 +/- 17.0 pg/ml (+/- SEM); n = 57] was significantly higher than that in normal subjects (37.6 +/- 1.9 pg/ml; n = 40). No significant correlation was found between plasma ANP and serum creatinine concentrations. CRF patients treated by maintenance hemodialysis had significantly higher plasma ANP levels than did nondialysis patients. Hemodialysis significantly decreased plasma ANP, and changes in plasma ANP levels after hemodialysis differed from those in serum creatinine concentrations. The mean serum creatinine concentration rose significantly 24 h after hemodialysis. In contrast, plasma ANP levels did not change in the first 24 h, but then rapidly increased. When ANP in predialysis plasma from patients with CRF was analyzed by reverse phase high performance liquid chromatography, the retention time of the main ANP peak coincided with that of synthetic human alpha ANP. These results suggest that expanded extracellular volume stimulates the secretion of ANP in CRF patients and that this increase in ANP release reflects a mechanism of compensation in volume homeostasis in man.     

Effect of atrial natriuretic peptide on adiponectin in patients with heart failure

BACKGROUND: The adipocyte-specific cytokine adiponectin, has cardioprotective effects, correlates with endogenous cardiac natriuretic peptides and adipocyte has guanylyl cyclase-A receptors of natriuretic peptides. AIMS: To evaluate the effect of carperitide (atrial natriuretic peptide; ANP) on plasma adiponectin in patients with heart failure. METHODS AND RESULTS: Seventy-five patients admitted to our hospital with decompensated heart failure were randomised (1:2) to nitroglycerin (group I: n = 23) or carperitide infusion (group II: n = 52). Blood samples were collected at baseline and after 7 days. Plasma levels of total and high-molecular weight (HMW) adiponectin, ANP and brain natriuretic peptide (BNP) were measured. There were no differences in baseline characteristics between the two groups. In group I, plasma levels of total and HMW adiponectin were significantly decreased (21.1+/-2.5 to 18.6+/-2.5 microg/mL, p<0.05, 12.3+/-1.8 to 10.8+/-1.7 microg/mL, p<0.05, respectively) concomitant with the decrease in plasma levels of ANP and BNP. In group II, plasma levels of total and HMW adiponectin were significantly increased (17.3+/-1.3 to 19.7+/-1.6 microg/mL, p<0.0001, 9.8+/-1.0 to 10.5+/-1.0 microg/mL, p<0.05, respectively) concomitant with the increase in ANP. CONCLUSIONS: These findings indicate that carperitide infusion increases plasma levels of total and HMW adiponectin in patients with heart failure.     

Prognostic importance of atrial natriuretic peptide in patients with chronic heart failure

Several circulating neurohormones have been shown to have prognostic significance in patients with chronic heart failure, but the relation between plasma levels of atrial natriuretic peptide and mortality in this disorder remains unknown. Plasma levels of immunoreactive atrial natriuretic peptide were measured in 102 patients in whom left ventricular ejection fraction, ventricular arrhythmias on ambulatory electrocardiographic recording and plasma levels of norepinephrine, renin activity, aldosterone and arginine vasopressin were also measured. Compared with patients with atrial natriuretic peptide concentrations below the median value of 125 pg/ml, patients with higher levels of the peptide had a higher plasma renin activity (8.9 +/- 1.8 versus 2.6 +/- 0.4 ng/ml per h) and plasma norepinephrine (858 +/- 116 versus 538 +/- 45 pg/ml), more frequent premature ventricular depolarizations (4,485 +/- 715 versus 2,004 +/- 495/day) and more advanced hemodynamic abnormalities (all p less than 0.05). During the subsequent 13 to 25 months of follow-up, patients with high levels of atrial natriuretic peptide had a significantly lower rate of survival than did those whose initial circulating peptide concentrations were normal or mildly increased (p = 0.01). These data indicate that, in patients with chronic heart failure, plasma atrial natriuretic peptide provides important prognostic information. This may relate to the ability of the hormone to reflect the interplay of several pathophysiologic factors that contribute to mortality in this disease.     

Bovine atrial natriuretic peptide in heart failure

The present study describes the concentration and molecular form of atrial natriuretic peptide (ANP) in Holstein dairy cattle with mild (bacterial endocarditis; BEC) or severe (dilated cardiomyopathy; DCM) heart failure. Significant increases in plasma concentration of ANP were observed in cattle with DCM (73.3 +/- 16.02 pmol/l, n = 4, P less than 0.01) and BEC (20.6 +/- 3.45 pmol/l, n = 7, P less than 0.05), when compared with those in control cattle (14.5 +/- 1.84 pmol/l, n = 12). The concentration of ANP in cattle with DCM was significantly (P less than 0.01) higher compared with that in cattle with BEC. Plasma concentration of ANP correlated significantly with right atrial pressure (r = 0.95, P less than 0.01) and left ventricular end-diastolic pressure (r = 0.84, P less than 0.01). Gel-permeation chromatography of ANP in plasma and the right atrium from control and cattle with BEC revealed a single peak corresponding to the elution position of authentic human ANP(99-126) in plasma, and two peaks corresponding to those of authentic human ANP(99-126) and pro-ANP in the atrial extract. In cattle with DCM, however, peaks corresponding to the elution positions of authentic human beta-ANP and/or pro-ANP were detected in addition to the peak corresponding to ANP(99-126). The content of ANP in the right atrium of cattle with DCM was significantly (P less than 0.05) increased compared with that in control cattle and those with BEC. The present study therefore suggests that the synthesis and secretion of ANP might be stimulated by atrial distention induced by increased atrial pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of atrial natriuretic peptide on glycerol induced acute renal failure in the rat.

Acute and chronic experiments were performed in rats to examine whether atrial natriuretic peptide (ANP) has any beneficial effects on glycerol-induced acute renal failure (ARF). ANP infusion (Atriopeptin III, 1.0 microgram/kg+0.2 microgram/kg/min) improved the renal blood flow (RBF) and the glomerular filtration rate (GFR), and induced profound natriuresis in the early stage of ARF. By contrast, ANP decreased RBF in the control rats. In addition to these acute hemodynamic effects, long-term beneficial effects of ANP were also observed. A 75-min infusion of ANP significantly lessened the degree of azotemia as well as the extent of renal histologic damage assessed 24 hours after the glycerol injection. These results indicate that ANP can afford partial protection against both acute renal dysfunction and the chronic course of the glycerol-induced ARF, suggesting that ANP may be useful in the treatment of ARF.     

利钾尿肽、心房钠尿肽在充血性心力衰竭患者中的变化

目的:研究利钾尿肽（KP）在和心房钠尿肽（ANP）充血性心力衰竭（CHF）中的变化及其意义。方法:用放射免疫分析方法测定50例患者发病不同时期血浆KP和ANP含量。结果:CHF患者在发病第1天血浆KP、ANP水平最高,随着病情的好转而逐渐降低,不同的心功能分级之间有显著差异,KP水平与左室射血分数呈显著负相关。结论:血浆KP水平在CHF病理生理中的改变有重要意义。     

Renal response to atrial natriuretic peptide in patients with advanced liver cirrhosis

Sodium retention in liver cirrhosis is thought to be due to, among other things, lack of a natriuretic factor or failure to respond to one. alpha-Human-atrial natriuretic peptide is a peptide that accounts partly or entirely for the circulating natriuretic activity in man. In the present study, we have evaluated the effects of the bolus administration of synthetic alpha-human-atrial natriuretic peptide (1 microgram per kg) to patients with liver cirrhosis and variable degrees of sodium retention. alpha-Human-atrial natriuretic peptide induced rapid and marked increases of diuresis and natriuresis in patients without sodium retention or with moderate retention. The results were comparable to those obtained in six healthy control subjects. Conversely, the diuretic and natriuretic effects of alpha-human-atrial natriuretic peptide were attenuated or completely blunted in patients with avid sodium retention. The two groups of patients differed not only in basal sodium excretion, but also in plasma renin activity and in plasma aldosterone levels, suggesting that the reduced responsiveness to atrial natriuretic peptide might be due to excessive antagonism by antinatriuretic factors. The direct relationship between baseline sodium excretion rate and that stimulated by human-atrial natriuretic peptide administration was consistent with this interpretation. In none of the subjects did plasma renin activity peptide and cortisol levels change after human-atrial natriuretic peptide, while plasma aldosterone slightly declined in cirrhotics. Blood pressure fell after the administration of the peptide, with the drug greater in cirrhotic than in normal subjects.(ABSTRACT TRUNCATED AT 250 WORDS)     

Increased plasma levels of atrial natriuretic peptide in patients with congestive heart failure

Atrial natriuretic peptide (ANP) is a recently discovered hormone,originating from atrial myocardium. The peptide (or family ofpeptides) induces potent diuretic/natiuretic, vasorelaxing andaldosterone inhibitory effects. We have investigated plasmaconcentrations of immunoreactive ANP in 10 patients with congestiveheart failure (CHF). Mean plasma ANP concentrations were morethan three times higher in CHF patients than in a matched controlgroup. High plasma ANP concentrations in pathophysiologicalconditions with a high preload combined with salt and waterretention is consistent with a physiological role of this hormoneto correct hypervolemia by causing natriuresis and diuresis.It is concluded that ANP homeostasis is altered in patientswith CHF and that this hormone may be of importance in the pathophysiologyof CHF.     

Atrial natriuretic peptide in patients with acute myocardial infarction without functional heart failure.

The purpose of the present study was to measure plasma levels of atrial natriuretic peptide (ANP) in patients with acute myocardial infarction without heart failure, and also to assess the temporal sequence of changes of plasma ANP during the first hours of recovery from myocardial infarction. The study was performed in 22 patients who were admitted to the Intensive Care Unit with the diagnosis of acute myocardial ischaemia that had an evolution of less than 6 h. Blood samples were drawn on admission and at 1, 8, and 24 h, and plasma concentrations of ANP, renin, aldosterone, epinephrine, norepinephrine and vasopressin were measured. Compared with control subjects, on admission patients showed increased plasma levels of ANP, as well as increased plasma renin activity (PRA), aldosterone, norepinephrine, epinephrine, dopamine, and antidiuretic hormone (ADH). ANP, but not renin or aldosterone plasma values, decreased with time, and there was a significant correlation between ANP and time after onset of pain. No increase in plasma creatinine was observed during the hospital stay, and the patients showed a negative fluid balance. No relationship was found between the location or extension of the infarction, or morphine treatment and ANP plasma levels. The high levels of ANP seem to counteract the haemodynamic and fluid-retention effects of the vasoconstrictive factors released after myocardial infarction.     

Control of atrial natriuretic peptide secretion in patients with severe congestive heart failure

Congestive heart failure (CHF) is marked by activation of multiple hormone systems that increased peripheral vasoconstriction and produce sodium and water retention. Plasma atrial natriuretic peptide (ANP) levels are frequently elevated in patients with severe CHF and may act to counterbalance these hormonal actions. To determine whether CHF patients maintain a physiological response to the presumed major stimulus to ANP secretion, atrial stretch, 22 CHF patients and 8 normal volunteers were studied. Atrial distention was produced in 10 CHF patients with a mannitol infusion and in 12 with lower body positive pressure. Eight normal volunteers also underwent a mannitol infusion. Both stimuli provoked increases in plasma ANP levels in the CHF patients, and the relative increase in plasma ANP after mannitol was similar in the CHF patients and the normal volunteers. We conclude that ANP secretion responds to atrial stretch in CHF patients, suggesting maintenance of the physiological release of this peptide.     

Attenuated renal excretory response to atrial natriuretic peptide in congestive heart failure in man.

The renal and hormonal effects of atrial natriuretic peptide given as a bolus injection (2.0 micrograms/kg) were studied in 12 patients with congestive heart failure before and after treatment with captopril for 4 weeks and in 13 healthy control subjects. Atrial natriuretic peptide caused a rise in urinary excretion of sodium and urinary flow in the controls, whereas no increases were observed in the patients. Both proximal and distal fractional reabsorption of sodium, as evaluated by the lithium clearance technique, decreased less in the patients than in the controls. Basal plasma concentrations of atrial natriuretic peptide and cyclic guanosine monophosphate (cGMP), and the basal urinary excretion of cGMP, were elevated in the patients. The increases in both plasma and urinary cGMP after administration of atrial natriuretic peptide were blunted in heart failure. Basal glomerular filtration rate and renal plasma flow were reduced, and filtration fraction increased, in the patients. A positive correlation (r = 0.958, P less than 0.01) was found between renal plasma flow and the relative increase in urinary excretion of sodium in the patients with heart failure. Treatment with captopril did not improve the natriuretic and diuretic effect of exogenous atrial natriuretic peptide, but resulted in an increase in filtration fraction after administration of atrial natriuretic peptide not present before captopril.(ABSTRACT TRUNCATED AT 250 WORDS)     

Circulating forms of human atrial natriuretic peptide in patients with congestive heart failure

To elucidate the circulating forms of human atrial natriuretic peptide (hANP) in patients with congestive heart failure (CHF), plasma samples obtained from 36 patients with CHF were analyzed and compared with those from normal subjects. Plasma concentrations of hANP-like immunoreactivity (LI) from normal subjects and patients with mild CHF (class I), as classified by the New York Heart Association (NYHA) functional criteria, did not differ (15 +/- 1 vs. 16 +/- 1 pmol/L, mean +/- SE), whereas plasma levels of hANP-LI in patients with moderate and severe CHF significantly (P less than 0.01) increased in relation to the severity of CHF (class II, 44 +/- 4 pmol/L; class III, 116 +/- 24 pmol/L; class IV, 141 +/- 21 pmol/L). Reverse-phase HPLC and gel permeation chromatography coupled with RIA for hANP revealed that the circulating forms of hANP-LI consisted of alpha-hANP, beta-hANP, and gamma-hANP in CHF, whereas alpha-hANP predominated in normal plasma. The percentage of beta-hANP in total hANP-LI as calculated from the chromatograms by gel filtration was greater in severe CHF (NYHA class III and IV) than those in mild CHF (NYHA class I and II), and apparently exceeded those of other forms. Successful medical treatment for CHF resulted in a marked reduction of total plasma hANP-LI levels with a concomitant disappearance or reduction of beta-hANP in 14 patients examined. These data suggest that beta-hANP and gamma-hANP are secreted from the failing human heart, possibly resulting from the augmented synthesis and/or the altered processing of hANP precursor in cardiocytes, and that circulating beta-hANP may serve as a potential marker for the severity of CHF in man.     

Relationship between B-type natriuretic peptide levels and ventilatory response during cardiopulmonary exercise test in patients with chronic heart failure

AIM: Aim of the study was to evaluate if brain natriuretic peptide (BNP) levels, a cardiac neurohormone well correlated with prognosis in chronic heart failure (CHF), are associated with enhanced ventilatory response to exercise, in ambulatory patients with intermediate peak oxygen uptake (PVO2). METHODS: Resting BNP was measured in 129 consecutive stable CHF patients with mild to moderate heart failure (90% New York Heart Association (NYHA) class II or III) and intermediate (10-18 mL/kg/min) PVO2, assessed during cardiopulmonary exercise test. Mean (SD) left ventricular ejection fraction (EF) and pulmonary systolic pressure (PAP) were 41 +/- 3% and 47 +/- 14 mmHg, respectively. The enhanced ventilatory response to exercise (EVR) was assessed as a slope of the relation between minute ventilation and carbon dioxide production (VE/VCO2 slope) > 35. RESULTS: Thirty-three over 129 patients (26%) had EVR. Mean BNP plasma level was 394 +/- 347 pg/mL. A significant correlation between BNP and EVR (r = 0.310; p < 0.01), was observed. In the logistic multivariate model, a BNP plasma level > 100 pg/mL had an independent predictive value for EVR (95% IC 1.68 to 10.5, Odds Ratio 4.23, p = 0.02). We found a significant correlation between BNP and PAP (r = 0.390; p < 0.001), and between PAP and EVR (r = 0.511; p < 0.01). CONCLUSIONS: In CHF patients with intermediate PVO2, plasma BNP is clearly related to the enhanced ventilatory response to exercise. In this subset, BNP levels could represent an effective alternative tool for the clinical assessment in patients with unreliable cardiopulmonary exercise test.