Atrial natriuretic peptide in diabetes mellitus patients with arterial hypertension]

The basal level of atrial natriuretic peptide (ANP) of the venous blood plasma was investigated in 105 diabetic patients with concomitant arterial hypertension (AH) as well as in 20 healthy persons of the same age. Analysis of the results of investigation was performed with respect to AH type (essential, atherosclerotic, nephrogenic) and expression of cardiac changes. An ANP level in diabetic patients without AH did not differ from that of the controls. In the presence of AH this level was increased 2-10-fold. The highest level of ANP was observed in patients with nephrogenic hypertension and marked cardiac disorders. The results obtained suggest the role of ANP in AH pathogenesis.     

Pulmonary arterial brain natriuretic peptide concentration and cardiopulmonary hemodynamics during exercise in patients with essential hypertension

Brain natriuretic peptide (BNP) is secreted through the coronary sinus of the human heart. The purpose of this study was to determine whether BNP secretion from the heart is stimulated by exercise and to examine the relationship between pulmonary arterial BNP concentrations and hemodynamic measurements, especially cardiopulmonary hemodynamics, during exercise in patients with essential hypertension. The exercise protocol consisted of three fixed workloads (25, 50, 75 W) on a bicycle ergometer in the supine position. The mean pulmonary arterial BNP level at rest was 14.8 +/- 4.1 pg/mL, and BNP values gradually increased with higher stages of exercise. At the maximum exercise stage, the BNP value increased to 40.9 +/- 6.5 pg/mL. Close correlations of pulmonary arterial pressure (PAP) and pulmonary arterial wedge pressure (PAWP) with pulmonary arterial BNP level were observed at four points at rest and during each stage of exercise. In contrast, heart rate, mean blood pressure, cardiac index (CI), and stroke index (SI) were not correlated with BNP values. Results suggest that cardiac secretion of BNP was increased during exercise in essential hypertensive subjects, and the observed increase of BNP may be related to elevated PAP and PAWP. The enhancement of BNP secretion during exercise in these patients may reflect increased redistribution of blood to the cardiopulmonary compartment.     

The effect of atrial septostomy on the concentration of brain-type natriuretic peptide in patients with idiopathic pulmonary arterial hypertension

Atrial septostomy has improved haemodynamics and clinical symptoms in selected patients with idiopathic pulmonary arterial hypertension. We found that, in 5 patients with idiopathic pulmonary arterial hypertension, septostomy resulted in decreased levels of brain-type natriuretic peptide, and improvement in symptoms of cardiac failure, suggesting that serial measurements of the peptide may have clinical utility.     

N-terminal brain natriuretic peptide in scleroderma-associated pulmonary arterial hypertension: reply

We read with interest the comments of Mathai and Hassoun, andagree that caution is required in using an NTproBNP level of     

Pulmonary hemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension

STUDY OBJECTIVES: Brain natriuretic peptide (BNP) blunts hypoxic pulmonary hypertension in animal models, but its acute hemodynamic effects in patients with pulmonary arterial hypertension (PAH) are not known. The aim of this study was to determine if human B-type natriuretic peptide is a safe and efficacious pulmonary vasodilator in patients with PAH and if the pulmonary hemodynamic effects are potentiated by phosphodiesterase inhibition. DESIGN: Open-label study. SETTING: Medical ICUs of three tertiary care hospitals in New England. PATIENTS: Thirteen consecutive adult patients undergoing right-heart catheterization and a pulmonary vasodilator trial for the initial evaluation of PAH. INTERVENTIONS: Patients were administered inhaled nitric oxide (iNO), i.v. epoprostenol, and a 3-h infusion of BNP alone and 1 h after an oral dose of the phosphodiesterase-5 inhibitor sildenafil. RESULTS: iNO and sildenafil alone decreased mean pulmonary artery pressure (mPAP) without a significant fall in pulmonary vascular resistance (PVR). Epoprostenol decreased both mPAP and PVR. BNP alone had no significant effect on pulmonary hemodynamics, but the combination of sildenafil plus BNP decreased mPAP and PVR for up to 6 h after stopping BNP. The decrease in mPAP with sildenafil plus BNP (+/- SE) was greater than after 1 h of sildenafil alone (44.6 +/- 3.8 to 40.6 +/- 3.9 mm Hg, p = 0.027). An acute vasodilator response, defined as a decrease in mPAP > 10 mm Hg and end mPAP < 40 mm Hg, was seen in 0 of 8 patients with iNO, 1 of 13 patients with epoprostenol, 0 of 13 patients with BNP, and 4 of 12 patients with sildenafil plus BNP. BNP decreased mean systemic arterial pressure (5.6 +/- 2.8 mm Hg) but had no effect on cardiac output or systemic vascular resistance. CONCLUSIONS: A 3-h BNP infusion does not significantly improve pulmonary hemodynamics in most patients with PAH but is well tolerated and augments the acute pulmonary vasodilator effect of sildenafil.     

N-terminal brain natriuretic peptide in scleroderma-associated pulmonary arterial hypertension.

We read with great interest the report by Williams et al.¹ regardingN-TproBNP levels in patients with scleroderma-associated pulmonaryarterial hypertension (SSc-PAH). In studying a large cohortof scleroderma patients, the authors found that     

Atrial natriuretic peptide during pacing in controls and patients with coronary arterial disease

At rest, during cardiac catheterization, aortic plasma levels of immunoreactive atrial natriuretic peptide did not differ between 10 controls with atypical chest pains and normal coronary arteries and 9 patients with stable angina pectoris and coronary arterial disease (55.2 +/- 19.8 vs. 64.8 +/- 19.8 pg/ml, NS). Nor did atrial natriuretic peptide values differ between the two groups during or after atrial pacing (150 beats/minute), which induced electrocardiographic and metabolic signs of acute myocardial ischaemia in the patients with coronary arterial disease but in none of the controls. Pacing, when carried out for more than 300 seconds, induced an increase of plasma atrial natriuretic peptide that correlated with duration of pacing (r = 0.80, P less than 0.001), and similarly in controls and patients with coronary arterial disease. In a second part of the study, which included 2 controls and 2 patients with coronary arterial disease, post-pacing coronary sinus concentrations of atrial natriuretic peptide were 10-20 times higher than peripheral levels (415- greater than 890 pg/ml). The concentration of atrial natriuretic peptide rose as blood from the caval veins (34 +/- 7 pg/ml) entered the right atrium (56 +/- 24 pg/ml), but thereafter was unchanged in the pulmonary artery (51 +/- 3 pg/ml) and the aorta (46 +/- 9 pg/ml). In conclusion, the results gave no evidence for ischaemic heart disease without congestive cardiac failure to be associated with altered levels of atrial natriuretic peptide. It was confirmed that atrial pacing stimulates the secretion of atrial natriuretic peptide which is produced by the heart and released via the coronary sinus into the circulation.     

Relationship between the structure-functional state of the heart and brain natriuretic peptide level in patients with arterial hypertension

We studied relationship between structure-functional parameters of left and right cardiac chambers and N-terminal pro-brain natriuretic peptide (NT-proBNP) level in 118 patients with arterial hypertension (AH) (35 men, 83 women) and 17 healthy volunteers. Methods comprised 24-hour arterial pressure monitoring (APM), two-dimensional echocardiography (echoCG), Doppler echoCG, and tissue echoCG of mitral and tricuspid atrioventricular annuli, treadmill test, 6-min walk test, and measurement of NT-proBNP level in blood plasma. In patients with AH blood plasma NT-proBNP level was significantly higher than in a group of healthy persons of similar age. Elevation of this biochemical marker was accompanied by significant change of characteristics of remodeling of left and right parts of the heart, abnormalities of left ventricular diastolic function according to transmitral blood flow, disturbances of left ventricular diastolic and systolic function according to tissue Doplerography data. Comparative analysis of structure-functional parameters of the heart and NT-proBNP level in patients with AH allowed to reveal more significant changes of parameters of diastolic and systolic remodeling, local and global diastolic and systolic left ventricular function in patients with NT-proBNP levels more than 306 mol/ml. Factors determining NT-proBNP level in patients with AH were age, free right ventricular wall thickness, and body mass index.     

Atrial natriuretic peptide concentrations and pulmonary hemodynamics in patients with pulmonary artery hypertension

To define the relationship between plasma levels of immunoreactive atrial natriuretic peptide (IR-ANP) and hemodynamic parameters in patients with chronic pulmonary artery hypertension, we measured plasma concentrations of the peptide in 15 patients during right heart catheterization. Eleven patients had chronic obstructive pulmonary disease and 4 had pulmonary vascular disease of diverse etiology. At rest, plasma concentrations of IR-ANP positively correlated with mean pulmonary artery pressure (r = 0.70, p less than 0.01) and pulmonary vascular resistance (r = 0.88, p less than 0.001), but not with right atrial pressure. Nine of these patients, all with chronic obstructive pulmonary disease, were also evaluated during exercise. Plasma concentrations of IR-ANP increased from 131 +/- 22 to 191 +/- 30 pg/ml (p less than 0.003) at maximal exercise, whereas pulmonary artery pressure increased from 29 +/- 1.5 to 56 +/- 2.5 mm Hg and right atrial pressure from 5 +/- 1 to 13 +/- 2 mm Hg. Increases of plasma IR-ANP concentrations correlated with changes in pulmonary artery pressure and right atrial pressure but not with changes in pulmonary capillary wedge pressure. These findings suggest that ANP is released in response to an increase in pulmonary artery pressure and are consistent with the hypothesis that ANP could modulate the pulmonary vascular tone in patients with pulmonary artery hypertension.     

前列地尔脂微球载体对老年肺心病并发心力衰竭者血浆BNP、ET-1水平的影响

目的 探讨老年慢性肺心病伴心力衰竭时血浆脑钠素(BNP)、内皮素-1(ET-1)水平变化及前列地尔脂微球载体注射液(Lipo-PGE1,商品名:凯时)对其影响. 方法 老年慢性肺心病伴心力衰竭患者28例,随机分为治疗组(14例)和常规治疗组(14例).常规治疗组为降肺动脉压、强心、利尿剂、血管扩张剂等药物并加用鼻导管给氧治疗.治疗组在常规内科治疗同时加用Lipo-PGE1注射液治疗,分别观察治疗10 ～ 14 d后2组患者临床症状、体征、心率(HR)、呼吸频率(RR)、血压、血氧饱和度( SaO2)、肺动脉压(PAP)和左室射血分数(LVEF)以及血浆BNP、ET-1变化. 结果 与常规治疗组比较,治疗组治疗10 ～ 14 d后,患者临床症状与体征改善明显,其SaO2和LVEF显著升高(P＜0.05),PAP、HR、RR显著下降(P＜0.05).Lipo-PGE1治疗后血浆BNP、ET-1水平随心衰的纠正而显著降低(P＜0.01),与LVEF呈显著负相关(P＜0.01),与PAP呈显著正相关(P＜0.05). 结论 Lipo-PGE1在改善老年慢性肺心病伴心力衰竭患者心功能和降低PAP的同时,也降低患者血浆BNP、ET-1水平,提示Lipo-PGE1可通过多环节对老年慢性肺心病心力衰竭治疗过程发挥作用.     

Atrial natriuretic peptide lowers pulmonary arterial pressure in patients with high altitude disease

The authors' previous studies have demonstrated that IV administration of atrial natriuretic peptide (ANP) produces a dose dependent decrease in pulmonary arterial pressure in rats adapted to chronic hypoxia. To examine the effects of ANP on chronic hypoxic pulmonary hypertension in man, alpha-human ANP (200 micrograms) was infused (20 micrograms/min X 10 min) into the right atrium via a Swan-Ganz catheter in four patients with pulmonary hypertension of high altitude. Following the infusion, pulmonary arterial pressure fell gradually and remained depressed for 1 hour. Peak reductions in pulmonary arterial systolic pressure (PASP) and mean pulmonary arterial pressure (MPAP) were 23% and 30%, respectively. Systemic arterial pressure, cardiac output and cardiac index also tended to decrease, but these changes did not reach statistical significance. The data suggest that ANP is useful in the treatment of chronic hypoxic pulmonary hypertension in man.     

维生素D缺乏与高血压病患者血清NT pro BNP浓度的关系

目的:研究高血压病患者中维生素D的缺乏与血清N末端脑钠尿肽原（NT-pro-BNP）浓度的关系。方法:选取2009年～2012年住院高血压病患者,根据血清25-羟维生素D［25(OH)D］浓度由高到低将入选患者分为4组:A组:对照组25(OH)D浓度≥30 ng/ml;B组:20 ng/ml<25(OH)D浓度<30 ng/ml;C组:10 ng/ml<25(OH)D浓度<20 ng/ml;D组:25(OH)D浓度≤10 ng/ml,测定血清NT-pro-BNP浓度,并作受试者血清各指标与血清NT-pro-BNP浓度相关性的分析。结果: B组和C组血清NT-pro-BNP浓度较对照组没有显著性差异。D组血清NT-pro-BNP浓度较对照组明显升高,差异有统计学意义（P<0.05）,D组血清NT-pro-BNP浓度较C组升高,差异有统计学意义（P<0.05）,即随着血清25(OH)D浓度的降低其血清NT pro BNP浓度显著升高。受试者血糖、血钙、总胆固醇、三酰甘油、糖化血红蛋白（HbA1C）、同型半胱氨酸、肌酐、甲状旁腺素与血清NT pro-BNP浓度没有相关性。结论:维生素D的缺乏明显增加高血压病患者发生心力衰竭的风险。     

N-terminal-pro-brain natriuretic peptide as a haemodynamic marker in idiopathic pulmonary arterial hypertension.

Patients with idiopathic pulmonary arterial hypertension usually undergo acute vasodilator tests with nitric oxide (NO) for haemodynamic evaluation and therapeutical planning. The aim of this study was to evaluate the link between the variation of N-terminal (NT)-pro-brain natriuretic peptide (BNP) levels and haemodynamic parameters during the acute vasodilator test. A total of 22 idiopathic pulmonary arterial hypertension patients who underwent acute vasodilator tests were studied. Blood samples were collected at baseline and after 30 and 60 min of NO inhalation. NT-pro-BNP levels were measured in each sample. A receiver-operating characteristic curve was used to evaluate the capability of the NT-pro-BNP level variation during NO inhalation in recognising nonresponders. To distinguish responders from nonresponders, the increase of the NT-pro-BNP (0% as cut-off value) determined a 50% specificity and 100% sensitivity (positive predictive value of 38% and a negative predictive value of 100%). These results suggest that N-terminal-pro-brain natriuretic peptide was able to distinguish nonresponder patients with the acute vasodilator test. N-terminal-pro-brain natriuretic peptide may be an interesting additional biological tool in the evaluation of idiopathic pulmonary arterial hypertension patients.     

Atrial natriuretic peptide response to postural changes in patients with left atrial hypertension

Plasma atrial natriuretic peptide (ANP), cyclic guanosine monophosphate(GMP) and renin activity (PRA) were measured in 13 patientswith mitral stenosis 24 h before and 48 h after balloon valvotomyresulting in a fall in LA pressure from 23.4 ± 2.2 to10.5 ± 0.8 mmHg (P<0.01). Before treatment, plasmaANP was higher during ambulation (128.1 ± 18.5 pg ml^–1)than in the supine posture (93.3± 15.0 pg ml^–1;P<0.01) and did not diminish after return to the erect posture(86.4± 14.1 pg ml^–1). A physiological responsewas restored after valvotomy with ANP plasma levels of 49.2± 7.8pg ml^–1 in the initial ambulant period, 63.1± 12.6 pg ml^–1 in the supine posture and 44.6 ±8.7 pg ml^–1 in the final erect posture. Postural variationsof cyclic GMP were parallel to those of ANP. In contrast, LAhypertension did not abolish PRA postural response. During thethree successive periods of ambulation, supine posture and erectposture PRA was 5.4± 10, 2.8 ± 0.6 and 5.5±1.2ng h^–1 ml^–1, respectively, before treatment,whereas after treatment the values measured were 10.3 ±2.9, 2.3 ± 0.7 and 7.0 ± 2.5 ngh^–1 ml^–1respectively. Variations of plasma ANP, cyclic GMP and PRA inresponse to postural changes were also studied in 10 healthyvolunteers and in 12 uraemic patients with high plasma ANP.Similar physiological results were obtained in these two controlgroups, suggesting that the dysregulation of ANP response inpatients with high LA pressure was not related to the high valuesof plasma ANP. In conclusion, persistent elevation of plasmaANP in response to postural changes appears to be the consequenceof LA hypertension.     

Impact of essential hypertension and primary aldosteronism on plasma brain natriuretic peptide concentration

Introduction. Brain natriuretic peptide (BNP) has important role in the diagnosis and management of heart failure. Data on the impact of blood pressure (BP) on BNP are controversial. In primary aldosteronism (PA), BNP production can be affected by both hypertension and specific endocrine mechanisms. This study was aimed at investigating the impact of hypertension and hyperaldosteronism on plasma BNP levels. Methods. Plasma BNP concentration, casual and 24-h BP and echocardiographic indices were assessed in 40 patients with moderate to severe essential hypertension (EH), 40 BP-matched patients with PA, and 40 age- and sex-matched healthy controls. Results. BNP levels in PA and EH groups did not differ significantly and were higher compared with those in controls [median and interquartile range 26 (13-48) pg/ml, p = 0.01, and 23 (9-32) pg/ml, n.s., vs 14 (6-26) pg/ml in controls]. Remarkably elevated BNP was observed only in three PA and two EH patients, all having significant left ventricular (LV) hypertrophy. BNP levels in PA and EH groups correlated weakly with casual and 24-h BP, interventricular septal thickness and LV mass index (LVMI). Diastolic BP and LVMI were identified as the strongest independent determinants of BNP (p = 0.002 and p = 0.01, respectively). Conclusions. Both PA and EH patients had modest and mutually comparable elevation of BNP, which was independently determined by diastolic BP and LVMI. Both subtypes of PA (aldosterone-producing adenoma and bilateral adrenal hyperplasia) had similar effect on BNP production. Specific impact of hyperaldosteronism on BNP was not confirmed.     

扩张性心肌病与心绞痛患者心肌营养素-1与脑尿钠肽的变化

目的 :比较扩张性心肌病 （DCM）与稳定型 （SA）、不稳定型心绞痛 （U A）患者外周血心肌营养素 - 1与脑尿钠肽的水平。方法 :选择 DCM和 SA,UA患者各 30例 ,并选择 30例匹配的正常人作为对照组 ,检测心肌营养素 - 1（CT-1）和脑尿钠肽 （BNP）。结果 :3组患者 CT- 1较正常对照组均明显增高 （P<0 .0 1） ,且 DCM,U A组较 SA组也明显升高 （P<0 .0 5 ） ;DCM与 UA组的 BNP较正常组明显升高 （P<0 .0 1） ,而 SA组无显著差异 （P>0 .0 5 ）。DCM组与UA组的 CT- 1和 BNP水平无显著差异 （P>0 .0 5 ）。结论 :CT- 1在 DCM与 U A的病程发展中起到重要作用 ;对于不稳定型心绞痛 ,CT- 1可能与 BNP相关。     

Characterization of brain natriuretic peptide in long-term follow-up of pulmonary arterial hypertension

STUDY OBJECTIVES: Pulmonary arterial hypertension (PAH) leads to substantial morbidity and mortality. Noninvasive parameters in the follow-up assessment of PAH could be helpful in clinical decision making. The brain natriuretic peptide (BNP) has been shown to correlate with the functional status and prognosis of these patients and could be a valuable parameter in this respect. The aim of our study was to investigate whether BNP levels could reflect clinical and hemodynamic changes, including the response to therapy during long-term follow-up in patients with PAH. STUDY DESIGN: We measured pulmonary hemodynamics, functional parameters including the 6-min walk distance (6MWD), and plasma BNP levels at baseline and after a mean (+/- SEM) follow-up period of 12.6 +/- 1.5 months in patients with PAH. RESULTS: In group A (n = 18), with decreasing BNP levels mean pulmonary artery pressure (PAP) and pulmonary vascular resistance (PVR) decreased (PAP, 60.89 +/- 3.44 to 53.47 +/- 3.24 mm Hg; PVR, 1,207.47 +/- 111.75 to 942.35 +/- 103.15 dyne.s.cm(-5); p < 0.01) and 6MWD increased (408.24 +/- 29.57 to 470 +/- 25.54 m; p < 0.01). In group B (n = 12), with increasing BNP levels mean PAP and PVR increased (PAP, 52 +/- 3.31 to 60.17 +/- 5.03 mm Hg; PVR, 946.13 +/- 115.35 to 1,236.6 +/- 180.23 dyne . s . cm(-5); p < 0.01) and mean 6MWD decreased from 463.64 +/- 27.77 to 367.27 +/- 38.87 m (p < 0.05). Comparing groups revealed statistically significant differences regarding changes in PAP (group A, -11.58 +/- 3.57%; group B, +13.29 +/- 5.44%; p = 0.001) and PVR (group A, -19.21 +/- 5.87%, group B, +30.35 +/- 7.72%; p < 0.001). Correlations existed between the changes in BNP levels and pulmonary hemodynamics. CONCLUSION: We concluded that BNP levels parallel changes in pulmonary hemodynamics and functional parameters, including the 6MWD, in PAH patients. Consequently, we suggest BNP as a parameter for the follow-up assessment of PAH patients.     

Analysis of endothelin-1 and endothelin-1 receptor A gene polymorphisms in patients with pulmonary arterial hypertension

This study analyses the frequency and the potential role of two polymorphisms, the +134del/insA, located in the gene encoding for Endothelin-1 (EDN1), and the His323His in the gene encoding for Endothelin receptor type A (EDNRA) in a cohort of 98 consecutive patients with pulmonary arterial hypertension from two different Cardiology Units (Mid-South of Italy), and in 100 healthy Caucasian subjects randomly recruited from the same area. Cardiac anatomy and function were analysed by non invasive diagnostic imaging techniques (Echocardiography standard m-mode, 2D, colour-Doppler) and by invasive studies (cardiac catheterization). Molecular screening of the region of interest was performed by automated sequencing. At univariate analysis, patients with the His323His TT genotype show a lower cardiac index (2 ± 0.6 vs. 2.3 ± 0.6; p = 0.05) and a higher indexed pulmonary vascular resistance (18.8 ± 9.6 vs. 14.2 ± 6.9; p = 0.01) at cardiac catheterization. A logistic multivariate model shows idiopathic disease (p = 0.01; OR = 3.8; CI = 1.3-11) and indexed pulmonary vascular resistances (p = 0.01; OR = 1.1; CI = 1-1.2) as independent predictors of TT genotype. Our findings may suggest a potential link between specific genotypes in the EDNRA gene and susceptibility for PAH.