Increased brain natriuretic peptide and atrial natriuretic peptide plasma concentrations in dialysis-dependent chronic renal failure and in patients with elevated left ventricular filling pressure

Brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) plasma concentrations were measured in patients with dialysis-dependent chronic renal failure and in patients with coronary artery disease exhibiting normal or elevated left ventricular end-diastolic pressure (LVEDP) (n = 30 each). Blood samples were obtained from the arterial line of the arteriovenous shunt before, 2 h after the beginning of, and at the end of hemodialysis in patients with chronic renal failure. In patients with coronary artery disease arterial blood samples were collected during cardiac catheterization. BNP and ANP concentrations were determined by radioimmunoassay after Sep Pak C₁₈ extraction. BNP and ANP concentrations decreased significantly (P < 0.001) during hemodialysis (BNP: 192.1 ± 24.9, 178.6 ± 23.0, 167.2 ± 21.8 pg/ml; ANP: 240.2 ± 28.7, 166.7 ± 21.3, 133.0 ± 15.5 pg/ml). The decrease in BNP plasma concentrations, however, was less marked than that in ANP plasma levels (BNP 13.5 ± 1.8%, ANP 40.2 ± 3.5%; P < 0.001). Plasma BNP and ANP concentrations were 10.7 ± 1.0 and 60.3 ± 4. 0 pg/ml in patients with normal LVEDP and 31.7 ± 3.6 and 118.3 ± 9.4 pg/ml in patients with elevated LVEDP. These data demonstrate that BNP and ANP levels are strongly elevated in patients with dialysis-dependent chronic renal failure compared to patients with normal LVEDP (BNP 15.6-fold, ANP 2.2-fold, after hemodialysis; P < 0.001 or elevated LVEDP (BNP 6.1-fold, ANP 2.0-fold, before hemodialysis; P < 0.001), and that the elevation in BNP concentrations was more pronounced than that in ANP plasma concentrations. The present results provide support that other factors than volume overload, for example, decreased renal clearance, are also involved in the elevationin BNP and ANP plasma levels in chronic renal failure. The stronger elevation in BNP concentrations in patients with chronic renal failure and in patients with elevated LVEDP and the less pronounced decrease during hemodialysis suggest a different regulation of BNP and ANP plasma concentrations.[/ p]Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide - LVEDP left ventricular end-diastolic pressure Correspondence to: C. Haug     

Regional cardiac expression and concentration of natriuretic peptides in patients with severe chronic heart failure

The purpose of this study was to examine the regional cardiac mRNA expression and concentration of brain natriuretic peptide (BNP) and atrial natriuretic peptide (ANP) in relation to the circulating peptide concentrations in patients with chronic heart failure (CHF). The myocardial mRNA levels and peptide concentrations of BNP and ANP were analysed in seven different regions of the heart from patients undergoing cardiac transplantation. Autopsy samples from individuals without known cardiovascular disease were used as controls. The plasma levels of natriuretic peptides and their N‐terminal propeptides, Nt‐proBNP and Nt‐proANP, were measured in the CHF patients and healthy volunteers. In the autopsy specimens, the atrial regions appeared to contain the highest peptide levels for BNP as well as ANP, the atrioventricular ratio being 12–262 and 72–637‐fold, respectively. In the CHF patients there was a relative shift towards the ventricle for BNP, reducing the atrioventricular ratio to 6–16‐fold. The circulating concentrations of BNP/Nt‐proBNP in the CHF patients correlated closely to the BNP mRNA expression in most myocardial regions including the left ventricle (r=0.72, P < 0.001). For circulating concentrations of ANP/Nt‐proANP, such correlation were limited to the left atrium free wall (r=0.66, P < 0.002). Thus, of the two natriuretic peptides, BNP/Nt‐proBNP may be a better reflector of left ventricular overload.     

急性心肌梗死患者血浆BNP、ANP、ET和CRP水平变化

为观察急性心肌梗死(AMI)患者血浆中脑钠肽(BNP)、内皮素(ET)、C-反应蛋白(CRP)和心钠素(ANP)水平变化, 探讨AMI发病机制,为诊断、治疗及预后判断提供依据, 应用酶联免疫及免疫放射分析法对46例AMI患者治疗前后和30名对照者血浆中的BNP、ET、CRP、ANP水平进行检测.结果显示, AMI患者血浆中BNP、ET、CRP、ANP治疗后均明显下降, 与治疗前比较有显著性差异(P＜0.01); AMI患者BNP、ET、CRP、ANP水平明显高于对照组(P＜0.01); BNP与CRP治疗前水平变化比较呈正相关r=0.847, 治疗后呈明显的下降趋势, 其相关系数为r=0.654; AMI患者治疗前后ANP与ET比较呈正相关, 但经溶栓和相应的支持治疗后ANP基本恢复到正常水平(P＞0.05),而BNP、ET、CRP水平虽然下降明显, 但与对照组比较仍有明显差异(P＜0.05).结论: AMI患者血浆中BNP、ANP、ET、CRP水平的变化说明其参与了急性心肌梗死发生、发展, 特别是冠状动脉粥样斑块的形成和(或)破裂及血栓形成, 其炎症因子是主要因素.因此, 四项指标的观察分析对AMI诊断、治疗、预后判断具有重要意义.     

2型糖尿病血管病变时血浆ANP、BNP及CNP的变化及临床意义

目的：探讨血浆心钠素(ANP)、脑利钠肽(BNP)、C型利钠肽(CNP)在2型糖尿病血管病变时的变化及其临床意义。方法:应用酶联免疫吸附法(ELISA)测定正常对照组(9例)、2型糖尿病无血管病变组(34例)及2型糖尿病血管病变组(23例)血浆proANP、BNP fragment及NT-proCNP浓度，分析各组间血浆利钠肽水平的变化及相关因素。结果:2型糖尿病血管病变组血浆ANP、BNP明显高于另外2组（P<0.01），而血浆CNP明显降低（P<0.01），2型糖尿病血管病变组各亚组(微血管病变组、大血管病变组及微血管合并大血管病变组)间血浆利钠肽水平无明显差异（P>0.05）。2型糖尿病血管病变组血浆ANP与BNP间存在显著正相关（r=0.309, P<0.05），ANP与CNP（r=-0.374, P<0.05）以及BNP与CNP（r=-0.653, P<0.01）间存在显著负相关。结论:血浆ANP、BNP及CNP的联合检测可以作为简便、价廉、可靠的糖尿病血管病变的筛选指标。     

Atrial natriuretic peptide levels and pulmonary artery pressure awake, at exercise and asleep in obstructive sleep apnoea syndrome

Elevated nocturnal plasma atrial natriuretic peptide (ANP) levels were found in patients with obstructive sleep apnoea (OSA). The purpose of our study was to examine the secretion of ANP during the night and to measure changes in oxygen saturation, pulmonary artery pressure and intrathoracic pressure swings in patients with OSA. Moreover, we analysed the secretion of ANP and the pulmonary artery pressure in different behavioural states, e.g. awake, at exercise and asleep. Consecutive apnoeas in non-rapid eye movement (NREM) sleep at the beginning, middle and end of the sleep study were analysed in six patients with obstructive sleep apnoea. In addition, we measured the plasma levels of ANP. The apnoea duration was significantly longer (P< 0.05) at the middle of the sleep study than at the beginning or end. Correspondingly, the end-apnoeic oxygen saturation and end-apnoeic oesophageal pressure were both significantly lower (P< 0.05) in the middle of the sleep study than at the beginning or end. No significant differences were found in the end-apnoeic systolic transmural pulmonary artery pressure (P(PATM)) and the levels of ANP. Evaluation of the ANP levels during different behavioural states revealed that the asleep levels were slightly, but not significantly, higher than the awake levels (0.235+/-0.088 vs. 0.207+/-0.057 nmol/L). However, the highest levels were found during exercise (0.334+/-0.170 nmol/L) with a significant difference compared with the awake and asleep levels. These data suggest that volume effects may be a potent factor in liberating ANP during exercise, but the role of OSA in ANP secretion when asleep is questionable.     

COPD患者血清ANP、BNP和CNP测定及其临床意义

目的：探讨慢性阻塞性肺疾病（COPD）患者血清心钠素（ANP）、脑钠肽（BNP）、C型钠尿肽（CNP）水平的变化及其临床意义。方法：采用放射免疫分析79例COPD患者和36例健康对照组血清ANP、BNP和CNP水平,并进行统计分析。结果：COPD组血清ANP、BNP和CNP水平显著地高于健康对照组（t=3.6841,P〈0.01;t=11.70,P〈0.01;t=2.177,P〈0.05）,但Ⅰ、Ⅱ、Ⅲ和Ⅳ级组间血清ANP、BNP和CNP水平方差检验无显著性意义（F=2.123、F=1.515、F=0.165,P均〉0.05）。相互间相关性分析揭示：ANP、BNP和CNP三者间均呈显著正相关（r=0.369,P〈0.01;r=0.354,P〈0.01;r=0.426,P〈0.01）。住院期间死亡的患者血清ANP、BNP和CNP水平显著地高于好转出院的患者（t=5.149,P〈0.01;t=4.875,P〈0.01;t=2.830,P〈0.01）。结论：COPD患者血清ANP、BNP和CNP显著升高,且与病人的稳定情况、肺动脉压力及预后相关。     

Plasma levels of atrial natriuretic peptide are raised in essential hypertension during low and high sodium intake

Summary Plasma levels of -human atrial natriuretic peptide (hANP) were measured in 17 patients with primary hypertension (11 females, 6 males, aged 22–61; blood pressure systolic 154±7 mmHg, diastolic 92±4 mmHg) and in 9 normotensive controls (4 males, 5 females, aged 20–71; blood pressure systolic 117±4 mmHg, diastolic 76±2 mmHg) during unrestricted sodium diet, at the 4th day of a low sodium intake (40–60 mEq/day) and at the 6th day of sodium loading (280–320 mEq/day) both after an overnight rest and after 4 h of upright posture. In the controls, plasma levels of hANP at 8:00 a.m. were lowered from 73±11 to 49±7 pg/ml during low sodium diet and increased to 128±37 pg/ml after high salt intake. Plasma ANP levels were significantly lower after 4 h of upright posture during unrestricted, low and high sodium intake. In the hypertensive group, plasma ANP levels were elevated during unrestricted diet (203±43 pg/ml), during the low sodium period (139±31 pg/ml), and after high sodium intake (267±63 pg/ml) compared to the controls. All levels were lowered by upright posture. The absolute decrease was more pronounced compared to the normotensives, the relative decline was similar in both groups. In the hypertensives, plasma ANP levels significantly correlate with systolic and diastolic blood pressure (r=0.468,r=0.448,P<0.05) and with urinary aldosterone during unrestricted diet (r=0.536,P<0.05). There was an inverse correlation between plasma ANP levels and plasma renin concentration during low and high sodium intake (r=–0.469,r=–0.496,P<0.05).These studies demonstrate raised circulating plasma ANP levels in patients with essential hypertension. The modulation of ANP by different sodium intake and by upright posture is maintained similar to the changes in plasma ANP in normotensive controls. Raised ANP levels in the hypertensives are correlated with low renin secretion and high aldosterone excretion. High ANP levels, therefore, might indicate sodium retention in essential hypertension.Abbreviation ANP atrial natriuretic peptide Supported by a grant from Ministerium für Wissenschaft und Forschung, NRW     

Plasma brain natriuretic peptide levels in coronary heart disease with preserved systolic function

Abstract. We evaluated the circulating levels of brain natriuretic peptide (BNP) in stable angina, unstable angina, and myocardial infarction relating hormone levels to extension of coronary disease and number of vessels involved after angiographic examination. We studied 86 patients consecutively undergoing angiographic coronary examination and echocardiographic evaluation for coronary heart disease. These included 15 control subjects (group 0), 21 with stable angina (group I), 26 with unstable angina (group II), and 24 with non-Q myocardial infarction (group III). Patients with heart failure, a history of myocardial infarction, or recent myocardial damage with electrocardiographic S-T elevation were excluded. BNP levels in patients with unstable angina and myocardial infarction were significantly increased with respect to the group with stable angina (P<0.01). There were no differences between the groups with unstable angina and myocardial infarction. Analysis of peptide levels in relation to the number of involved vessels demonstrated a significant increase in patients with three-vessel disease compared with subjects with one or two vessels involved (P<0.03); among subjects with mono-vessel disease, patients with left descendent anterior stenosis had a moremarked BNP elevation than subjects with stenosis in other regions (P<0.01). Hence, BNP levels appear to be elevated in coronary disease, especially in acute coronary syndromes, even in the absence of systolic dysfunction. BNP levels also seem to be related to the severity of coronary atherosclerosis and number of vessels involved. BNP could prove a novel marker for risk stratification, not only in heart failure but also in coronary heart disease.     

EH患者血清利钠多肽及血栓素B_2水平的分析

目的：探讨原发性高血压（EH）患者血清ANP、BNP、CNP及TXB2水平的变化及其临床意义。方法：30例EH患者和正常人对照组分为2组;不同EH分期Ⅰ、Ⅱ、Ⅲ期分为3组,将测定结果进行统计分析。四项血清标志物均采用放射免疫分析。结果：EH患者组ANP、BNP、CNP及TXB2四项血清指标水平均较对照组升高非常显著（P均〈0.01）。Ⅰ期组EH患者血清ANP、CNP及TXB2三项血清标志物与对照组比较差异均无显著性（P均〉0.05）,而血清BNP则显著高于对照组（P〈0.05）;Ⅱ期组患者ANP水平显著高于Ⅰ期组和对照组（P〈0.05）,而BNP、CNP和TXB2三项血清标志物则非常显著高于Ⅰ期组和对照组（P均〈0.01）。Ⅲ期组结果显示,ANP、BNP、CNP和TXB2四项血清标志物均非常显著地高于Ⅱ期组、Ⅰ期组及对照组（P均〈0.01）,相关分析结果显示,患者ANP、BNP和CNP三项指标与自身的平均动脉压呈显著正相关（r=0.298,P〈0.01;r=0.409,P〈0.01;r=0.412,P〈0.01）。结论：本文四项血清指标水平显著升高,测定数据的变化与EH的发病及病情进展有关。     

Dysregulation of pulsatility in aging IV. Pulsatile signaling and cardiovascular aging: functions and regulation of natriuretic peptide signaling

Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones connecting heart and kidney and playing a key role in hydromineral and hemodynamic homeostasis. In contrast with the renin-angiotensin-aldosterone system, circulating ANP and BNP are not temporally related with rapid eye movement (REM)-nonREM sleep cycles, autonomic activity, or blood pressure. Cardiac natriuretic peptides are secreted in a pulsatile manner, with short periods of 20-48 min, in normal as well as in pathological conditions. The frequency of pulses seems to be unchanged with aging, whereas the absolute amplitude of the oscillations seems to increase, most likely as a result of an increase in the plasma hormone levels observed in elderly. Enhanced cardiac secretion and decreased degradation partly explain the higher ANP and BNP concentrations observed in elderly. Despite higher levels, the natriuretic system seems to loose efficiency at the renal site in elderly. This more probably relies on reduced target organ responsivity and not on deeply altered hormone secretion. Here we review the impact of aging on the renal effects of the natriuretic peptides, and point out the lack of knowledge on the precise interactions between the ultradian rhythms of the systems involved in salt and water balance in elderly. Additional studies focusing on potential age-induced alterations of the intracellular signaling pathway are now needed.     

利尿钠肽在诊断心力衰竭中的应用价值

探讨利尿钠肽的水平对心力衰竭（心衰）早期诊断的应用价值。采用放免法、ELISA法检测了129例心衰患者血浆中的心房利尿钠肽（ANP）、脑利尿钠肽（BNP）、N末端脑钠肽前体蛋白（NT-proBNP）水平,并与30例健康对照者进行了比较分析。结果显示,心衰患者血浆中的ANP、BNP、NT-proBNP显著高于健康对照组,且均随着NYHA分级的升高而逐渐增加,其含量在NYHA Ⅳ级时到达最高,心衰患者的血浆ANP、NT-proBNP水平与LVEF呈明显负相关。检测血浆中的ANP、BNP、NT-proBNP含量简便、快捷,可用于心衰诊断及NYHA分级判断。     

ANP gene expression in rat hearts during hypoxia

 It is unclear whether the increase in plasma atrial natriuretic peptide (ANP) concentration during hypoxia is due to direct, hypoxia-induced upregulation of ANP secretion in the heart, or to pressure overload of the right ventricle (RV) following hypoxia-induced pulmonary hypertension. To test the hypothesis that hypoxia leads to an early upregulation of the ANP gene, we examined the influence of acute and prolonged inspiratory hypoxia (6 h, 1 or 3 weeks) on the expression of ANP messenger ribonucleic acid (mRNA) in rat heart and compared the results with the expression of the ANP gene after acute pressure overload induced by experimental coarctation of the main pulmonary artery. As a molecular marker for hypertrophy we determined the ratio of α- and β-myosin gene expression. Hypoxia increased systolic RV pressure from 20.0 ± 1.6 mmHg to 27.8 ± 1.6 mmHg (P < 0.01) and 41.6 ± 2.1 mmHg (P < 0.05) after 1 and 3 weeks hypoxia respectively. The ANP plasma concentration did not change significantly after 6 h or 1 week: 232 ± 21 pg/ml (control), 246 ± 25 pg/ml (6 h), 268 ± 25 pg/ml (1 week), but increased significantly after 3 weeks hypoxia (446.8 ± 99.56 pg/ml; P < 0.05). ANP mRNA levels in different regions of the heart did not change after 6 h or 1 week hypoxia. After 3 weeks hypoxia ANP mRNA had increased 2.7-fold in the RV (P < 0.05), 4.2-fold in the left ventricle (LV, P < 0.05), 3.5-fold in the septum (S, P < 0.05) and about 1.4-fold in the right (n.s.) and left atrium (n.s.). Relative ventricular masses increased significantly only for the RV (190%, P < 0.05) during hypoxia. The β/α-myosin mRNA ratio did not change after 6 h hypoxia but, contrary to ANP gene expression, increased after just 1 week (6.1-fold in RV, 7.8-fold in LV, 6-fold in S; P < 0.05) and was more pronounced in the RV after 3 weeks (9.4-fold in RV, 7.6-fold in LV, 9.1-fold in S; P < 0.05). The increase in the β/α-myosin mRNA ratio in the LV contrasts with a lack of increase in relative ventricular mass. Acute pressure overload in the RV after pulmonary arterial banding significantly increased ANP-mRNA and the β/α-myosin mRNA ratio after 1 day in the RV. In the LV ANP mRNA was unchanged. The delayed upregulation of the ANP gene suggests that hypoxia per se is not a significant stimulus for ANP gene expression in the heart and that hypoxia-induced ANP-gene expression in the heart is regulated predominantly by the increase in RV afterload due to hypoxia-induced increased pulmonary pressure. The upregulation of ANP and β-myosin mRNA in the LV during chronic hypoxia has yet to be elucidated. Received: 5 November 1996 / Received after revision and accepted: 24 January 1997     

The human leucocyte antigen DQB1*0602 allele is associated with electroencephelograph differences in individuals with obstructive sleep apnoea syndrome

Human leucocyte antigen (HLA) DQB1*0602 allele, a well‐known genetic risk factor for narcolepsy, has been associated with sleep parameters in healthy subjects. We aimed to assess the association of this allele with daytime sleepiness and altered sleep electroencephalogram characteristics in the general population and in patients with obstructive sleep apnoea syndrome (OSAS). Eight hundred and ninety‐four individuals from the Epidemiologic Study of Sleep were genotyped for the HLA DQB1*0602 allele. Full‐night polysomnography was performed, and daytime sleepiness was analysed according to the Epworth Sleepiness Scale. HLA‐DQB1*0602 allele‐positive and ‐negative subjects in the general population, as well as in patients with OSAS, exhibited similar sleep parameters and levels of daytime sleepiness. However, spectral analysis showed that allele‐positive individuals with OSAS exhibited higher theta power during sleep Stage 1 (P < 0.05) in occipital derivations, and lower delta power during sleep Stages 1 and 2 (P < 0.01) compared with individuals negative for the allele, even after correction for potential confounders as age, sex, body mass index and European ancestry. No significant differences in the electroencephalogram variables were found in individuals without OSAS. The data highlight the HLA‐DQB1*0602 as a potential genetic factor influencing sleep physiology in individuals diagnosed with OSAS.     

Atrial natriuretic peptide response to endurance physical training in the rat

Summary The effect of an endurance physical training programme on the plasma and atrial natriuretic peptides (ANP) and on renal glomerular ANP receptors was evaluated in male normotensive Wistar rats. Maximal O₂ uptake was significantly greater in the endurance trained (117.1 Ml O₂ · kg^–1 · min^–1, SEM 6.18 versus the control rats 84.2 ml O₂ · kg^–1 · min^–1, SEM 4.88, P<0.01. In addition, various muscle oxidative enzymes were also significantly higher in endurance trained animals. An increase in resting plasma [ANP] was observed after 11 weeks of physical training (40.02 pg · ml^–1, SEM 7.07 vs 22.8 pg.ml^–1, SEM 3.83, P<0.05). Glomerular ANP receptor density was lower in trained rats (272 fmol · mg^–1 protein, SEM 3.1 vs 380 fmol · mg^–1 protein, SEM 6.1, P < 0.05), whereas atrial tissue [ANP] was not significantly different between controls and trained animals. However, in trained rats, circulating [ANP] was closely correlated with left atrial [ANP] (r = –0.92, P<0.05). Resting systolic blood pressure had not changed at the end of this physical training programme. It is considered that under physiological conditions ANP may be involved in long-term extracellular fluid volume homeostasis through the regulation of renal glomerular ANP receptors, and that the left atrium might play a significant role in this long term fluid volume control.     

Hormone changes induced by 37.5-h head-down tilt (−6°) in humans

Endocrine regulation of hormones and electrolytes during 37.5 h of –6° head down tilt (HDT) was studied in 13 men. The acute effects of simulated weightlessness are today well documented, but no study has been made concerning the hormone changes between 12 h and 2 days of HDT. Plasma volume showed a maximal increase of 9.23 (SEM 1.97) % after 6.5 h (P<0.01) and had returned to prestudy levels after 13.5 h of HDT. From 1.5 h to 4 h of HDT, C-terminus and N-terminus atrial natriuretic peptide (ANP) concentrations in plasma were increased by about 50% (P<0.01) and thereafter declined to pre-HDT levels. Plasma renin activity (PRA) was decreased by 47% (P<0.05) after 4 h of HDT; PRA increased after 23.5 h to 60%; noradrenaline concentration decreased immediately and remained low up to 37.5 h. Diuresis and natriuresis were evident during the 1st day of HDT, resulting in a marked increase in the urinary Na⁺. These results showed that the initial hormone (ANP, PRA) changes during HDT did not last more than 13.5 h and that after 24 h a new state would seem to have been established to adapt the body to hypovolaemia.     

房间隔缺损患者行经封堵术后右心室容量及血浆心钠素的变化

目的:观察房间隔缺损(ASD)封堵术后右心室容量及血浆心钠素(ANP)的变化。方法:对23例成功行经导管ASD封堵术的患者,分别于封堵术前、术后3天取静脉血,采用放射免疫法测定血浆ANP浓度;并于术前、术后3天行心脏三维超声心动图检查,测量右心室腔容量;并对ANP与肺动脉压(PAP)、右心室腔容量、右室射血分数进行相关分析。结果:ASD封堵术后3天血浆ANP浓度较术前明显降低(101.89±35.80ng/Lvs153.46±74.55ng/L,P<0.01);封堵术后3天右心室容量较术前明显缩小,差异有统计学意义(P<0.05),相关分析显示:ASD患者血浆ANP浓度与PAP(r=0.74)、右心室舒张末期容量(r=0.50)、收缩末期容量(r=0.50)分别呈正相关(P均<0.05)、与右室射血分数呈负相关(r=-0.38,P<0.05)。结论:ASD封堵术后血浆心钠素浓度明显降低,右心室腔明显缩小。     

Cardiac natriuretic peptide hormones during artificial cardiac pacemaker stimulation and left heart catheterization

Summary Brain natriuretic peptide (BNP) is synthesized and released predominantly in the ventricular myocardium whereas atrial natriuretic peptide (ANP) is produced mainly in the atria. This study evaluated whether artificial pacemaker stimulation or left heart catheterization results in specific changes in BNP and ANP plasma levels. Both BNP and ANP responded sensitively to changes in pacemaker stimulation (single-chamber pacemakers; pacing rates of 72 and 92/min) and during the left heart catheterization procedure. However, whereas higher pacing resulted in a more pronounced increase in plasma BNP levels, a stronger ANP release followed catheterization. This incongruous rise in ANP and BNP plasma concentrations points to at least partly independent mechanisms govering the release of BNP and ANP.Abbreviations ANP atrial natriuretic peptide - BNP brain natriuretic peptide     

Comparison of three measures of quality of life outcome in the evaluation of continuous positive airways pressure therapy for sleep apnoea

Treatment of obstructive sleep apnoea (OSA) with nasal continuous positive airway pressure (NCPAP) has become a standard treatment since its introduction in 1981. Following such treatment the apnoeas disappear, sleep quality improves as apparently do daytime symptoms of sleepiness. Sleepiness is an unusual symptom and its impact on conventional indices of quality of life has rarely been measured. To allow comparison of NCPAP therapy with treatments for other conditions, measurements of quality of life before and after treatment using standard techniques are required. It is not clear which of the standard measures is most suited to measuring the health gain from nasal NCPAP, and indeed whether the disability of excessive sleepiness is included in all such measures. This study looks at three well recognized quality of life measures in OSA, before and after NCPAP therapy; the Short Form 36 (SF-36), Functional Limitations Profile (FLP), and the EuroQol (EQ-5D). The results were compared with data from normal populations. One hundred and eight patients with OSA undergoing a therapeutic assessment of NCPAP completed the three quality of life questionnaires before and 5 weeks after commencing treatment. Over 90 subjects completed all sections of the three measures on both occasions. The SF-36 revealed substantial adverse effects on subjective health of OSA and that NCPAP treatment produced dramatic positive effects. For example, the effect sizes (difference in score, divided by SD of baseline score) in the Energy/Vitality dimension was 0.98 and for the overall Mental and Physical Component Scores, 0.76 and 0.57, respectively: an effect size over 0.5 is considered moderate and over 0.8 as large. The FLP data showed similar pre treatment decrements in quality of life and substantial improvements following NCPAP. The changes with treatment in the majority of the dimensions from both the SF-36 and FLP were statistically significant (P<0.01). In contrast the EQ-5D did not show significant improvements with therapy, presumably because of its failure to measure the aspects of quality of life related to severe sleep fragmentation and daytime sleepiness. In conclusion, this study has clearly shown considerable decrements in quality of life in patients with OSA, similar to other chronic disabling conditions. Furthermore, NCPAP therapy returns patients to a quality of life similar to the normal population.     

Long-term elevations of dietary sodium produce parallel increases in the renal excretion of urodilatin and sodium

The effects of dietary sodium intake on the renal excretion of urodilatin and of sodium were examined in six healthy male subjects. The 24-day study period was divided into three phases of 8 days each. Subjects Ingested 2.8 mequiv sodium (kg body weight)^–1 day^–1 during the first phase, 5.6 mequiv (kg body weight)^–1 day^–1 during the second phase, and 8.4 mequiv (kg body weight)^–1 day^–1 during the third phase. The excretion of both sodium (P<0.002) and urodilatin (P<0.006) increased in response to the increasing dietary sodium, while urine flow did not change. Urinary urodilatin excretion correlated closely with renal sodium excretion (P<0.001). Serum aldosterone levels (P<0.01) as well as serum renin levels (P<0.05) significantly decreased with increasing sodium intake. Plasma [Arg]vasopressin levels increased significantly (P<0.05). Plasma atrial natriuretic factor and cGMP levels as well as urinary cGMP excretion rates were unaltered by the changes in sodium intake. We conclude from these results that the renal natriuretic peptide, urodilatin, but not the main cardiac member of the natriuretic peptide family may be involved in the regulation of day-to-day sodium balance.     

Characterization of the 5′-flanking region and chromosomal assignment of the human brain natriuretic peptide gene

Brain natriuretic peptide (BNP) is a cardiac hormone that occurs predominantly in the ventricle, and synthesis and secretion of BNP are greatly augmented in patients with congestive heart failure and in animal models of ventricular hypertrophy. In order to elucidate the molecular mechanisms underlying the human BNP gene expression in the heart, the human BNP gene was isolated from a size-selected genomic minilibrary. The 1.9-kb human BNP 5-flanking region (–1813 to +110) contained an array of putative cis-acting regulatory elements. Various lengths of the cloned 5-flanking sequences were linked upstream to the bacterial chloramphenicol acetyltransferase (CAT) gene, and their promoter activities were assayed. The 1.9-kb promoter region showed a high-level CAT activity in cultured neonatal rat ventricular cardiocytes. When the CT-rich sequences (–1288 to –1095) were deleted, the high-level activity was reduced to approximately 30%. The 399-bp BNP 5 flanking region (–289 to +110) showed approximately 10% activity of the 1.9-kb region. Furthermore, using human-rodent somatic hybrid cell lines, the BNP gene was assigned to human chromosome 1, on which the atrial natriuretic peptide gene is localized. The present study leads to a better understanding of the molecular mechanisms for the human BNP gene expression in the heart.Abbreviations ANP Atrial natriuretic peptide - AP-1 Activator protein-1 - BNP Brain natriuretic peptide - CAT Chloramphenicol acetyltransferase