Combined inhibition of angiotensin II and endothelin suppresses the brain natriuretic peptide response to developing heart failure

2004 ◽  
Vol 106 (6) ◽  
pp. 569-576 ◽  
Author(s):  
Miriam T. RADEMAKER ◽  
Chris J. CHARLES ◽  
Eric A. ESPINER ◽  
Chris M. FRAMPTON ◽  
M. Gary NICHOLLS ◽  
...  

Blockade of AngII (angiotensin II) and ET (endothelin)-1, established and potential therapeutic strategies respectively, for heart failure, may have an adverse effect on the cardiac secretion of the natriuretic peptides, hormones with actions beneficial in this disease. The present study investigates the roles of AngII and ET-1 in regulating the stretch-induced release of the natriuretic peptides during the development of heart failure. On seven separate days, eight sheep underwent incremental left ventricular pacing (155, 190 and 225 beats/min for 90 min each) with concurrent infusions of a vehicle control, AngII, ET-1, AngII+ET-1, losartan [AT1 (AngII type 1) receptor antagonist], bosentan (ETA/ETB receptor antagonist) or losartan+bosentan. Pacing-induced rises in LAP (left atrial pressure) were amplified by the simultaneous administration of separate AngII and ET-1, and attenuated following blockade of the peptides, with maximum effects observed during combined treatments. Although these changes in atrial pressure were paralleled by concomitant alterations in circulating levels of both ANP (atrial natriuretic peptide) and BNP (brain natriuretic peptide), the plasma natriuretic peptide/atrial pressure relationship tended to be augmented by AngII and ET-1 and diminished by their blockade. A significant difference was demonstrated between the enhanced plasma BNP response to increasing LAP during combined AngII+ET-1 administration and decreased response during losartan+bosentan treatment (P<0.05). A similar, but non-significant, trend was evident for ANP. The present study indicates dual AngII/ET-1 blockade diminishes BNP (and to a lesser extent ANP) secretion in developing heart failure, suggesting that augmentation of the natriuretic peptide system during the combination of these therapies may be of benefit.

2010 ◽  
Vol 120 (5) ◽  
pp. 207-217 ◽  
Author(s):  
Miriam T. Rademaker ◽  
Christopher J. Charles ◽  
Iain C. Melton ◽  
A. Mark Richards ◽  
Christopher M. Frampton ◽  
...  

Monitoring of HF (heart failure) with intracardiac pressure, intrathoracic impedance and/or natriuretic peptide levels has been advocated. We aimed to investigate possible differences in the response patterns of each of these monitoring modalities during HF decompensation that may have an impact on the potential for early therapeutic intervention. Six sheep were implanted with a LAP (left atrial pressure) sensor and a CRT-D (cardiac resynchronization therapy defibrillator) capable of monitoring impedance along six lead configuration vectors. An estimate of ALAP (LAP from admittance) was determined by linear regression. HF was induced by rapid ventricular pacing at 180 and 220 bpm (beats/min) for a week each, followed by a third week with daily pacing suspensions for increasing durations (1–5 h). Incremental pacing induced progressively severe HF reflected in increases in LAP (5.9 ± 0.4 to 24.5 ± 1.6 mmHg) and plasma atrial (20 ± 3 to 197 ± 36 pmol/l) and B-type natriuretic peptide (3.7 ± 0.7 to 32.7 ± 5.4 pmol/l) (all P<0.001) levels. All impedance vectors decreased in proportion to HF severity (all P<0.001), with the LVring (left ventricular)-case vector correlating best with LAP (r2=0.63, P<0.001). Natriuretic peptides closely paralleled rapid acute changes in LAP during alterations in pacing (P<0.001), whereas impedance changes were delayed relative to LAP. ALAP exhibited good agreement with LAP. In summary, impedance measured with an LV lead correlates significantly with changes in LAP, but exhibits a delayed response to acute alterations. Natriuretic peptides respond rapidly to acute LAP changes. Direct LAP, impedance and natriuretic peptide measurements all show promise as early indicators of worsening HF. ALAP provides an estimate of LAP that may be clinically useful.


2018 ◽  
Vol 24 (2) ◽  
pp. 14-21
Author(s):  
V.O. Ruzhanskaya ◽  
V.G Sivak ◽  
O.O. Sakovych ◽  
V.M. Zhebel

One of the main etiological causes of development of heart failure is essential hypertension. The diagnosis of heart failure is usually made on the basis of comprehensive analysis of medical history, sonographic and biochemical examination. Normal ejection fraction does not exclude dyspnea of cardiac origin. Objective: to determine the role of galectin-3 as a marker of structural and functional changes of the myocardium in males with essential hypertension and CHF, carriers of polymorphic AT1R genes, residents of Podillya region of Ukraine. In this contingent, the surveyed were studied сoncentrations of galectin-3 and brain natriuretic peptide (BNP), parameters of central and systemic hemodynamics in carriers of polymorphic variants of angiotensin II type 1 receptor gene (АТ1R) - individuals with no cardiovascular pathology (n=79), male patients with II-III degree essential hypertension (EH) and hypertrophy of the myocardium (n=62), and essential hypertension (n=50) complicated by chronic heart failure (CHF), residents of Podillya region of Ukraine, were studied. Genotyping of АТ1R gene was performed using polymerase chain reaction. Galectin-3 and brain natriuretic peptide levels were determined by enzyme immunoassay. Structural and functional parameters of myocardium were assessed by ultrasound using the apparatus “RADMIR ULTIMARA”. Statistical analysis of the results obtained was done on personal computer using standard statistical package Statistica 10.0. The data are represented as mean values (M) and standard deviations (±m). Carriers of C allele of angiotensin II type 1 receptor gene were found to be dominating among the males with essential hypertension and resultant myocardial hypertrophy. Concentrations of galectin-3 and brain natriuretic peptide were significantly higher in men with essential hypertension and essential hypertension associated with chronic heart failure, as compared to those with no cardiovascular diseases, as well as the carriers of C allele of angiotensin II type 1 receptor gene. It was found that concentrations of study biomarkers were higher in individuals with severe and eccentric left ventricular hypertrophy, as well as in those with decreased ejection fraction of the left ventricle. Therefore, those biomarkers can be used in complex diagnosis of left ventricular hypertrophy in essential hypertension and the development of chronic heart failure in such patients.


Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Deddo Moertl ◽  
Martin Huelsmann ◽  
Joachim Struck ◽  
Andreas Gleiss ◽  
Alexandra Hammer ◽  
...  

Background: Although natriuretic peptides are increasingly used for the management of chronic heart failure (CHF), there are sparse comparative data. Therefore, we compared the importance of influencing factors, the ability to detect left ventricular systolic dysfunction, and the prognostic power of midregional pro-atrial natriuretic peptide (MR-proANP), B-type natriuretic peptide (BNP), and aminoterminal pro-B-type natriuretic peptide (NT-proBNP) in patients with chronic heart failure. Methods and Results: MR-proANP, using a new assay directed at the midregion of aminoterminal-proANP, was compared with BNP and NT-proBNP, using conventional assays, in 797 patients with CHF. All three natriuretic peptides were independently influenced by left ventricular ejection fraction (LVEF), glomerular filtration rate (GFR), and the presence of ankle edema. Area under receiver-operator characteristic curves for detection of an LVEF <40% were similar between MR-proANP (0.799 [0.753– 0.844]) and BNP (0.803 [0.757– 0.849]), and NT-proBNP (0.730 [0.681– 0.778]. During a median observation time of 68 months, 492 patients died. In multiple Cox regression analysis each natriuretic peptide was the strongest prognostic parameter among various clinical variables, but proportion of explained variation showed that NT-proANP was a significantly stronger predictor of death than NT-proBNP and BNP (Figure ). Conclusions: Despite similarities in influencing factors and detection of reduced LVEF, MR-proANP outperformed BNP and NT-proBNP in the prediction of death. A new assay technology and the high biological stability of MR-proANP are potential explanations for these findings.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Carlo Fino ◽  
Isabelle Piazza ◽  
Bruno Vito Domenico ◽  
Philippe Pibarot ◽  
Attilio Iacovoni ◽  
...  

Background and Objective: Surgical treatment of severe secondary ischemic mitral regurgitation (IMR) may improve symptoms and functional capacity, however there are few data on its effect on long-on the evolution of heart failure. Time-course changes in brain natriuretic peptide (BNP) are a good marker of the heart failure status and outcomes. We investigated the association between the exercise stress echocardiographic (ESE) parameters and the changes in brain natriuretic peptide (BNP) following surgery for secondary IMR. Methods: We prospectively analyzed data on 50 patients (median age: 67, 61-64 y; EF: 35, 34-40%), undergoing mitral valve annuloplasty or replacement and coronary artery bypass graft (CABG). A valve annuloplasty with undersized ring was performed in 20 patients (40%) and a replacement in 30 (60%). A six minute walking test (6-MWT), BNP levels and ESE were performed at 1 year and at median follow-up (FU) of 6 years (4-7). Results: BNP level was: 388 (329-441) pg/ml before surgery, 175 (142-743) pg/ml at 1 y, and 123 (100-979) pg/ml at last FU (p=0.2). The relative changes of BNP from baseline to last FU significantly correlated with exercise tricuspid annulus plane systolic excursion (TAPSE) at last FU (r= -0.7, p<0.001), with preoperative and FU exercise LVEF, respectively ( r=-0.7 p= 0.01) (r=-0.93, p<0.001).On multivariable analysis, preoperative exercise EF was strongly and independently associated with independent BNP levels at last FU and with the changes in BNP from baseline to last FU. Conclusions: Despite surgical treatment of severe secondary IMR, BNP levels progressively increased over time in nearly 50% of the patients. Lower preoperative and 1-year FU exercise-stress EF was associated with increased levels of BNP during FU..


2008 ◽  
Vol 37 (2) ◽  
pp. 174-179
Author(s):  
Mugdim Bajric ◽  
Fahir Barakovic ◽  
Nusret Sinanovic ◽  
Denis Mrsic

The most significant discoveries in the area of heart failure are the recognition of natriuretic peptide system and its multiple effects on cardiac structure and function with special effect on its natriuretic and hemodynamic processes. First information’s that heart, beside its function as a mechanical pump also has an important endocrine functions, exists for over 50 years. Chemical structure of atrial natriuretic peptide has been identified in 1984. and four years later a brain natriuretic peptide has been discovered owning its name because it has been identified in pig brain. Primary site of brain natriuretic peptide synthesis in heart has been identified in 1991. Natriuretic peptides are neither neurohormones that influence body fluid homeostasis through natriuretic and diuretic effect; regulate vascular tone by decreasing angiotensine II level and they inhibit nor epinephrine synthesis and increase parasympathetic tone. They are natural antagonists of renin-angiotensine-aldosteron system, and they have a great role in inhibition of ventricular hypertrophy and remodeling, protective effects in endothelial dysfunction are important; they increase effects of nitrite oxide, inhibit lipid deposition in vascular wall and inhibit thrombocyte activation, regulate coagulation and fibrinolytic processes as well. Natriuretic peptides clinical use is in early evaluation of heart failure, prognostic stratification and detection of systolic and diastolic dysfunction of left ventricle, assessment of prognosis during patient monitoring period, differential diagnosis of dyspnea, treatment adjustment and dosage titration, assessment during hospital admittance and discharge and forecast and reduction of coronary events.


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