The existence of low concentrations of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid which does not correlate with plasma ANP levels.

Atrial natriuretic peptide (ANP) concentrations within the reference interval have been reported in patients with alcoholic liver disease, chronic active hepatitis, and hepatocellular carcinoma. Markedly increased ANP concentrations, by contrast, have been found in patients with liver cirrhosis [3]. Exogenously administered ANP has been found to elevate the plasma concentration of its second messenger cyclic guanosine monophosphate (cGMP) in accordance with its physiological effects [4]. Therefore, cGMP increase in plasma can be regarded as a marker for the biological activities of ANP. Because of contradictory reports [2, 3, 5] on ANP in liver cirrhosis we investigated plasma ANP and cGMP concentrations to assess the biological activity of ANP in liver cirrhosis. Plasma ANP concentrations were determined in 124 healthy volunteers (72 males, 52 females) aged 20 64 years (40 _+ 12 years) and plasma cGMP concentrations in 147 healthy blood donors (92 males, 55 females) aged 15-62 years (34+_ 13 years). Plasma ANP and cGMP concentrations were determined in 15 patients with liver cirrhosis (7 males, 8 females) aged 31-69 years (54_+ 14 years). Five patients had ascites. The underlying cause of cirrhosis was cq-antitrypsin deficiency in 4 patients, alcohol abuse in 7, chronic hepatitis in 2, and unknown in 2. Creatinine concentrations in plasma were within the normal range (79.56 -+ 9.547 p.mol/1, range: 66.3-101.66 pmol/1) in all patients. Plasma cGMP concentrations were determined by radioimmunoassay (Amersham International, Amersham, Buckinghamshire, UK), and ANP concentrations in plasma were measured by means of a commercially available radioimmunoassay (Eiken, Tokyo, Japan) without extraction [1]. Results are expressed as mean _+ SD. Groups were compared statistically using Mann-Whitney U test; significance was defined as P<0.05. Plasma cGMP concentrations in patients with liver cirrhosis (4.448_+2.022 nmol/1, range 0.5-8.28 nmot/1, n = 15) did not differ significantly from those in healthy controls (4.637_+ 1.533nmol/1, range, 1.88~.04nmol/1, n=147, P=0.9426; Fig. 1). By contrast, plasma ANP concentrations were significantly higher in patients with cirrhosis (213.867_+83.032 ng/1, range 107-389ng/1, n=15) than in healthy controls (69.5_+ 26.05 ng/1, range 18-151 ng/1, n = 124, P=0.0001; Fig. 1). In the group of patients with liver cirrhosis no significant difference in plasma ANP (206.2_+59.437 versus 217.7-+95.422, P = I ) or plasma cGMP (5.656-+1.804 versus 3.777_+1.897, P=0.142) concentrations were detectable between patients with and patients without ascites. We found increased immunoreactive ANP concentrations without a concomitant increase in plasma cGMP in our patients with liver cirrhosis. In accordance with earlier reports we found no significant difference in plasma concentrations of ANP [3]

To compare the concentration of plasma atrial natriuretic peptide in patients with acute myocardial infarction with a healthy population and to determine whether a raised concentration of plasma atrial natriuretic peptide at admission was a predictor of mortality after acute myocardial infarction. Patients with acute myocardial infarction were divided into a group with no congestion (class I) and a group with congestion (class II-IV) according to their highest Killip classification in the first 24 hours after infarction. The concentration of plasma atrial natriuretic peptide was measured at admission. On the basis of the concentration of atrial natriuretic peptide measured in the healthy population, patients were separated into two groups: a group with a high (greater than 200 pg/ml) and a group with a low concentration of atrial natriuretic peptide (less than or equal to 200 pg/ml). The patients were followed for three years. 55 patients admitted to the coronary care unit within 12 hours of the appearance of symptoms of acute myocardial infarction were compared with 51 healthy individuals. Plasma atrial natriuretic peptide, Killip class, mortality. The patients had significantly higher concentrations of atrial natriuretic peptide than the healthy controls. Furthermore, patients with congestion had a significantly higher concentration of atrial natriuretic peptide than the uncongested group of patients. Total mortality was 34.5%. In the group with a low concentration of atrial natriuretic peptide the mortality was only 13.6%, whereas mortality was significantly higher (48.5%) in the group with a high concentration. The measurement of atrial natriuretic peptide separated the patients into low and high risk groups after acute myocardial infarction.

Natriuretic peptides and contractile reserve in dilated cardiomyopathy

The purposes of the present study are to demonstrate the presence of atrial natriuretic peptide (ANP) in canine cerebrospinal fluid (CSF) and to determine its origin as either the brain or atrium. Fifty-seven mongrel canines weighing from 7.5 to 23.0kg (male: 28, female: 29) were anesthetized with sodium pentobarbital (30mg/mg, iv) and were ventilated with a Harvard respirator. 16 canines (11.5 to 16.0kg) were used to examine the effect of endogenously increased plasma ANP level on the ANP concentration of the CSF in acute heart failure induced by experimental aortic regurgitation. Subsequently to examine the effect of exogenously increased plasma ANP level on the ANP concentration of the CSF, physiological and pharmacological doses of synthetic human alpha-ANP were continuously infused into the right ventricle (25ng/kg/min. and 250ng/kg/min., respectively) for 32 min. in 15 canines (8.0 to 23.0kg), only physiological dose (25ng/kg/min.) was infused for 180 min. in 8 canines (12.5 to 23.0kg). The concentrations of ANP in canine CSF and plasma were measured by our highly sensitive and specific radioimmunoassay (RIA). The molecular forms in the plasma, CSF and the atrium and hypothalamus tissues were determined by gel permeation chromatography (GPC). The ANP concentration in CSF was 2.8 +/- 1.2pg/ml (mean +/- SD), lower than that in the plasma which was 51.5 +/- 19.9pg/ml, and no correlation was found between them (r = 0.16, p = ns). Plasma ANP concentrations increased from 46.5 +/- 13.0pg/ml to 94.6 +/- 27.7pg/ml according to a rise of the left atrial pressure by experimental aortic regurgitation. However, no significant change was noted from 3.7 +/- 0.7pg/ml to 3.8 +/- 1.0pg/ml in CSF ANP concentrations during the aortic regurgitation. The ANP concentration in the CSF did not change significantly while the plasma ANP concentration greatly increased following each intravenous infusion of the synthetic alpha-ANP. Only a single peak corresponding to a low molecular weight form of ANP in the position of authentic alpha-ANP in the canine CSF was observed by GPC, while there were peaks for both low and high molecular forms of ANP in the canine plasma. Furthermore, both low and high molecular weight peaks were observed for the right atrium and hypothalamus tissue extracts by GPC, and those tissues of the right atrium and hypothalamus contained ANP concentrations of 1.97ng/mg wet tissue and 2.6pg/ml wet tissue, respectively. These results indicate the presence of ANP in canine CSF and that it does not come from blood that has seeped across the blood-CSF barriers but may originate in the brain.

The effect of recumbent rest on plasma atrial natriuretic peptide (ANP) concentration, mean blood pressure (MBP) and heart rate was studied in 26 normal human volunteers. Plasma ANP concentration, MBP and heart rate were determined after 10 min sitting and after 2, 5, 8, 15 and 30 min of recumbency. During the first 5 min of recumbency there were significant decreases in both MBP (p less than 0.001) and heart rate (p less than 0.001) compared with sitting. There was a small but significant fall in plasma ANP concentration (p = 0.02) after 30 min of recumbency compared with sitting. No further reduction in MBP or heart rate occurred after 5 min supine. The level of MBP following 5 min supine correlated significantly (r = 0.44; p = 0.02) with the plasma ANP concentration 25 min later. Blood pressure and heart rate are highly dependent on posture and relaxation, and plasma ANP concentration in lesser degree. It is necessary to wait for stable baseline values to develop before any comparisons between blood pressure and plasma ANP are done. If it is assumed that a causative relation exists between blood pressure and plasma ANP level, it appears there may be a delay of 20-30 min between a change in blood pressure and the physiological response of plasma ANP level. This observation may have implications for the interpretation of the relation between blood pressure and plasma ANP concentration in healthy individuals.

The present study aimed to investigate whether brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), cortisol and thyroid hormone concentrations change during hemodialysis in patients with chronic renal failure. Blood samples were withdrawn in 30 patients with chronic renal failure before hemodialysis, 2 hours after the beginning and at the end of hemodialysis. ANP and BNP concentrations were determined by radioimmunoassay after Sep Pak C18 extraction. Cortisol, T3, T4, FT4 and TSH serum concentrations were measured by enzyme immunoassay. BNP and ANP plasma levels were strongly elevated in patients with renal failure (BNP 22.4 fold, ANP 4.7 fold versus controls [n = 20]) and decreased significantly (p < 0.001) during hemodialysis (BNP [pg/ml]: 192.1 +/- 24.9, 178.6 +/- 23.0, 167.2 +/- 21.8; ANP [pg/ml]: 240.2 +/- 28.7, 166.7 +/- 21.3, 133.0 +/- 15.5). BNP plasma concentrations showed a stronger elevation than ANP plasma levels and a less pronounced decrease during hemodialysis (BNP: 13.5 +/- 1.8%, ANP: 40.2 +/- 3.5%, p < 0.001) which might in part be due to the longer half-life of BNP. Cortisol and TSH levels did not change significantly whereas T3, T4 and FT4 levels increased significantly (p < 0.001) during hemodialysis. Since corticosteroids and thyroid hormones stimulate natriuretic peptide release, these data suggest that the dialysis-induced decrease of ANP and BNP plasma concentrations is not augmented by a loss of cortisol or thyroid hormones during hemodialysis. The present data provide support that BNP and ANP plasma concentrations are sensitive indicators of the extracellular fluid volume status.(ABSTRACT TRUNCATED AT 250 WORDS)

The effect of thoracic irradiation on plasma and myocardial atrial natriuretic peptide (ANP) was studied in rat. The animals were irradiated with a dose of 20 Gy to the heart. After, 1, 12, 26 and 52 weeks, plasma ANP concentration and ANP in atrial and ventricular myocardium were determined. Plasma ANP levels were increased to 140% of control values from 3 months onwards and remained elevated for the next 9 months. Atrial ANP concentrations remained unaltered in the first 6 months post-treatment, but became reduced after 1 year to 37% of control values. Ventricular ANP concentration in irradiated rats rose 20-fold within 3 months, remained at that level up to 6 months and fell to six times control values at 1 year. An inverse relationship between plasma and atrial ANP concentration was found, while plasma and ventricular ANP concentrations were positively correlated. The results obtained in the present study suggest that in radiation-induced heart disease, plasma ANP concentration can be used as a marker for early stage cardiac dysfunction.

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)

The aim of this study was to determine the value of an increase in plasma atrial natriuretic peptide (ANP) concentrations during submaximal exercise as a predictor of return of sinus rhythm (SR), and of its maintenance over a period of 6 months after cardioversion (CV) of chronic atrial fibrillation (AF). The study group included 42 patients with AF (mean duration 7 +/- 7 months) and a controlled ventricular rate. They underwent submaximal exercise testing 24 hours before CV. Blood samples were collected at rest and at peak of exercise for measurement of plasma ANP concentrations. Thirty-five of 42 patients were successfully cardioverted to SR. At 6 months, 23 patients remained in SR, while 12 had recurrence of AF. The plasma ANP concentrations before CV increased insignificantly during exercise in patients with unsuccessful CV or with recurrence of AF (60.8 +/- 17.3 pg/mL to 64 +/- 13.5 pg/mL, NS). The mean increase in plasma ANP concentration during exercise was significantly greater in the 23 patients who remained in SR than in the 19 patients unsuccessfully cardioverted or with recurrence of AF (17.5 +/- 7.6 pg/mL vs 5.8 +/- 4.5 pg/mL, P < 0.01). In multivariate logistic regression analysis, an increase in ANP plasma concentration was independently associated with successful CV and maintenance of SR up to 6 months of observation. In patients with chronic AF an exercise-induced increase in ANP concentration predicts successful CV and maintenance of SR.

Several reports have demonstrated a close correlation between plasma atrial natriuretic peptide (ANP) concentration and atrial pressure in stable heart diseases. However, few studies have investigated whether plasma ANP concentration is a noninvasive indicator of hemodynamic parameters during the treatment of heart failure. Thus, we have studied the relationship between peripheral plasma ANP concentration and concurrent hemodynamic variables during the treatment of heart failure, and, in order to determine whether secretion of ANP is stimulated in this disease condition, we compared the plasma ANP concentration in the pulmonary artery with that in the peripheral veins. Studies were performed in each of 9 patients with acute heart failure due to myocardial infarction (Group A) or chronic heart failure (Group B), who were matched as closely as possible for treatment, age, sex and cardiac output. In group A, no significant correlation was found between plasma ANP levels and any measured hemodynamic variables. In group B, peripheral plasma ANP concentrations were significantly correlated with left atrial pressure (r = 0.82, p less than 0.01), but not with right atrial pressure (r = 0.56, p greater than 0.05). Furthermore, in group B ANP levels in pulmonary arterial plasma were consistently higher than those in peripheral venous plasma, whereas in group A the opposite was observed in expired cases. These results suggest that measurement of peripheral plasma ANP is a useful noninvasive method for estimating left atrial pressure during the treatment of chronic heart failure. However, plasma ANP concentration may not be a valid means of estimating hemodynamic parameters in acute heart failure due to myocardial infarction. In such cases, the increased secretion of ANP was not obvious, and there may be other factors, in addition to atrial pressure, that regulate cardiac secretion of ANP.

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.

Objective To investigate effects of hydration status and exercise intensity on plasma atrial natriuretic peptide (ANP) concentration in exercising horses. Animals 4 trained Standardbreds. Procedure Horses performed a 40-minute exercise test at 65 to 70% maximal heart rate (HRmax; no incline) and a 12-minute test at approximately 90% HRmax (3.5° incline). The 40-minute test was performed with ad libitum access to drinking water (normohydration), after water had been withheld for 24 hours (dehydration), and 30 minutes after 12 L of water at body temperature had been given via nasogastric tube (hyperhydration). The 12-minute test was only performed with normohydrated horses. Results Plasma ANP concentration was higher toward the end of exercise during hyperhydration than during the other 2 hydration states, and the area under the plasma ANP concentration curve was significantly greater during hyperhydration than during dehydration. The maximal plasma ANP value induced during the 12-minute test was similar to that of the 40-minute test. After the 12-minute test, plasma ANP concentration did not decrease during the first 30 minutes of recovery, whereas after the 40-minute test, plasma ANP concentration decreased by approximately 30% during the same period. Conclusions Hydration status can affect plasma ANP concentration in horses during submaximal exercise. Maximal plasma ANP concentration was similar at the 2 exercise intensities studied, but the postexercise return to baseline values differed. Clinical Relevance Changes in hydration status can cause alterations in plasma concentration of ANP, one of the hormones involved in the control of cardiovascular functions during exercise. (Am J Vet Res 1998;59:489–494)

目的 探讨血浆脑钠素(BNP)、心钠素(ANP)浓度变化对心力衰竭的诊断价值.方法 分别采用酶联免疫法和放射免疫法检测75例心力衰竭患者(NYHAⅡ～Ⅳ级)和25名健康对照者的血浆BNP和ANP浓度,同时采用纽约心脏病学会(NYHA)标准对心功能分级和用超声心动图检查评定患者心功能.结果 心力衰竭组血浆BNP浓度为(1 794.1±724.5) ng/L、ANP浓度为(948.5 ± 520.7) ng/L,与正常对照组BNP(90.5±55.8) ng/L、ANP(121.7±71.1 ) ng/L比较差异有统计学意义(P＜0.01).BNP浓度心功能Ⅱ级为(552.9 ±339.6) ng/L、Ⅲ级(1 303.9±566.4 ) ng/L、Ⅳ级(3 625.5±1 069.2) ng/L,两两比较差异有统计学意义(P＜0.05);ANP浓度Ⅱ级为(518.8±376.3) ng/L、Ⅲ级(1 061.9±521.3) ng/L、ⅣV级(1 264.7±798.1) ng/L,Ⅱ级与Ⅲ级、Ⅳ级比较差异有统计学意义(P＜0.05),而Ⅲ级和Ⅳ级比较差异无统计学意义(P＞0.05).左心室射血分数LVEF＞40%的患者BNP为(1 096.7±656.6) ng/L、ANP为(931.6±320.9 ) ng/L,LVEF＜40%的患者BNP(2 659.4±743.5 ) ng/L、ANP(974.3±555.6 ) ng/L,两组患者血浆BNP浓度差异有统计学意义(P＜0.05);而ANP差异无统计学意义(P＞0.05).BNP和ANP在受试者工作特征(ROC)曲线下的面积分别为0.97和 0.85,两者曲线下面积差异有统计学意义(P＜0.01).结论 血浆BNP比ANP对心力衰竭患者的诊断具有更高的准确性,BNP与超声心动图反映的血流动力学状况指标LVEF及NYHA分级具有较好的相关性,可以作为心力衰竭分级的一个良好的诊断指标。

The effect of a non selective and a cardio-selective beta-blocker on basal and exercise-stimulated plasma atrial natriuretic peptide concentrations in healthy volunteers has been studied. Nine healthy volunteers received single oral doses of 5 mg tertatolol, 100 mg atenolol or placebo, at one week intervals, in a double blind cross over trial. At rest plasma atrial natriuretic peptide, aldosterone, antidiuretic hormone and cyclic GMP concentrations and plasma renin activity were not modified by the treatments. During exercise plasma atrial natriuretic peptide concentrations were significantly increased by each treatment, the increment being significantly greater on beta-blockers than on placebo. The rise in atrial natriuretic peptide was 72% after placebo (from 24 to 42 pg/ml), 184% after atenolol (from 30 to 86 pg/ml), and 183% after tertatolol (from 34 to 95 pg/ml), respectively. Thus, the study has shown that in healthy subjects the plasma natriuretic peptide concentration is increased by exercise and that the increase is considerably and equally potentiated by selective and non selective beta-adrenoceptor blockade. The effect may be mainly due to a reduction in ventricular contractility with an increase in atrial pressure. The beta-blockers did not influence the resting plasma atrial natriuretic peptide levels, which suggests that in healthy subjects basal atrial natriuretic peptide secretion is not controlled via beta-receptors.

To evaluate and compare the clinical usefulness of plasma atrial natriuretic peptide (ANP) and cardiac troponin-I (cTnI) concentrations for assessment of disease severity in dogs with naturally occurring mitral valve disease (MVD). 316 dogs with MVD and 40 healthy control dogs. Each dog underwent a physical examination and echocardiographic and thoracic radiographic assessments. Blood samples were obtained and processed for measurement of plasma ANP and cTnI concentrations. Dogs with MVD were categorized into 3 groups (stages B1 [no clinical signs or evidence of cardiac enlargement], B2 [no clinical signs with evidence of cardiac enlargement], and C [history of congestive heart failure and pulmonary edema]) on the basis of American College of Veterinary Internal Medicine guidelines. Receiver operating characteristic curve analysis was used to evaluate the accuracy of plasma ANP and cTnI concentrations for assessment of MVD severity. Plasma ANP and cTnI concentrations increased as disease severity increased. Median plasma ANP concentrations for all 3 MVD groups and median plasma cTnI concentrations for the stage B2 and C groups were significantly greater than the corresponding concentrations for the control group. Plasma ANP concentration, but not cTnI concentration, appeared to be useful for detection of dogs with subclinical (stages B1 and B2) MVD, whereas both concentrations appeared useful for detection of dogs with stage C MVD. Results indicated that plasma ANP and cTnI concentrations should not be used independently to diagnose MVD but can be used to assess MVD severity and supplement echocardiographic findings.