Renin–angiotensin system and neprilysin

ESC CardioMed ◽  
2018 ◽  
pp. 161-167 ◽  
Author(s):  
João Pedro Ferreira ◽  
Patrick Rossignol
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renin Angiotensin System ◽  
Pharmacological Properties ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Inhibition ◽  
Clinical Syndromes ◽  
Neprilysin Inhibitor ◽  
Neprilysin Inhibition

The advent of drugs able to modulate the renin–angiotensin system (RAS), and more recently the neprilysin inhibitor sacubitril in combination with a RAS blocker, has improved the outcome of many cardiovascular and renal conditions. In particular, heart failure, post-myocardial infarction, and hypertension are the cardiovascular clinical syndromes in which RAS inhibition (and in heart failure, in combination with neprilysin inhibition) has greatly improved morbidity and mortality. This chapter aims to provide an appraisal of RAS and neprilysin inhibitors regarding their pharmacological properties with respect to mechanism(s) of action, pharmacokinetics, monitoring, adverse effects, and drug interactions.

Renin–angiotensin system and neprilysin

ESC CardioMed ◽  
2018 ◽  
pp. 161-167
Author(s):  
João Pedro Ferreira ◽  
Patrick Rossignol
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renin Angiotensin System ◽  
Pharmacological Properties ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Inhibition ◽  
Clinical Syndromes ◽  
Neprilysin Inhibitor ◽  
Neprilysin Inhibition

The advent of drugs able to modulate the renin–angiotensin system (RAS), and more recently the neprilysin inhibitor sacubitril in combination with a RAS blocker, has improved the outcome of many cardiovascular and renal conditions. In particular, heart failure, post-myocardial infarction, and hypertension are the cardiovascular clinical syndromes in which RAS inhibition (and in heart failure, in combination with neprilysin inhibition) has greatly improved morbidity and mortality. This chapter aims to provide an appraisal of RAS and neprilysin inhibitors regarding their pharmacological properties with respect to mechanism(s) of action, pharmacokinetics, monitoring, adverse effects, and drug interactions.

scholarly journals Angiotensin Receptor-Neprilysin Inhibition Based on History of Heart Failure and Use of Renin-Angiotensin System Antagonists

2020 ◽  
Vol 76 (9) ◽  
pp. 1034-1048 ◽  
Author(s):  
Andrew P. Ambrosy ◽  
Eugene Braunwald ◽  
David A. Morrow ◽  
Adam D. DeVore ◽  
Kevin McCague ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renin Angiotensin System ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
History Of ◽  
Neprilysin Inhibition

Brain “ouabain” and angiotensin II contribute to cardiac dysfunction after myocardial infarction

1999 ◽  
Vol 277 (5) ◽  
pp. H1786-H1792 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Baoxue Yuan ◽  
Bing S. Huang
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renin Angiotensin System ◽  
Volume Overload ◽  
Angiotensin System ◽  
Sympathetic Hyperactivity ◽  
Renin Angiotensin ◽  
Fab Fragments ◽  
The Brain

In chronic heart failure (CHF), sympathetic activity increases in parallel with the impairment of left ventricle (LV) function, and sympathetic hyperactivity has been postulated to contribute to the progression of heart failure. In the brain, compounds with ouabain-like activity (“ouabain,” for brevity) and the renin-angiotensin system contribute to sympathetic hyperactivity in rats with CHF after myocardial infarction (MI). In the present studies, we assessed whether, in rats, chronic blockade of brain “ouabain” or the brain renin-angiotensin system inhibits the post-MI LV dysfunction. In rats, an MI was induced by acute coronary artery ligation. At either 0.5 or 4 wk post-MI, chronic treatment with Fab fragments for blocking brain “ouabain” or with losartan for blocking brain AT1 receptors was started and continued until 8 wk post-MI using osmotic minipumps connected to intracerebroventricular cannulas. At 8 wk post-MI, in conscious rats, LV pressures were measured at rest and in response to volume and pressure overload, followed by LV passive pressure-volume curves in vitro. At 8 wk post-MI, control MI rats exhibited clear increases in LV end-diastolic pressure (LVEDP) at rest and in response to pressure and volume overload. LV pressure-volume curves in vitro showed a marked shift to the right. Intravenous administration of the Fab fragments or losartan at rates used for central blockade did not affect these parameters. In contrast, chronic central blockade with either Fab fragments or losartan significantly lowered LVEDP at rest (only in 0.5- to 8-wk groups) and particularly in response to pressure or volume overload. LV dilation, as assessed from LV pressure-volume curves, was also significantly inhibited. These results indicate that chronic blockade of brain “ouabain” or brain AT1 receptors substantially inhibits development of LV dilation and dysfunction in rats post-MI.

Effectiveness of angiotensin-neprilysin inhibitor treatment versus renin-angiotensin system blockade in older adults with heart failure in clinical care

Heart ◽  
2021 ◽  
pp. heartjnl-2021-319405
Author(s):  
Rishi J Desai ◽  
Elisabetta Patorno ◽  
Muthiah Vaduganathan ◽  
Mufaddal Mahesri ◽  
Kristyn Chin ◽  
...  
Keyword(s):  
Heart Failure ◽  
Older Adults ◽  
Fixed Effects ◽  
Clinical Care ◽  
Renin Angiotensin System ◽  
Fee For Service ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Neprilysin Inhibitor

ObjectiveTo evaluate the effectiveness of angiotensin receptor-neprilysin inhibitor (ARNI) versus renin-angiotensin system (RAS) blockade alone in older adults with heart failure with reduced ejection fraction (HFrEF).MethodsWe conducted a cohort study using US Medicare fee-for-service claims data (2014–2017). Patients with HFrEF ≥65 years were identified in two cohorts: (1) initiators of ARNI or RAS blockade alone (ACE inhibitor, ACEI; or angiotensin receptor blocker, ARB) and (2) switchers from an ACEI to either ARNI or ARB. HR with 95% CI from Cox proportional hazard regression and 1-year restricted mean survival time (RMST) difference with 95% CI were calculated for a composite outcome of time to first worsening heart failure event or all-cause mortality after adjustment for 71 pre-exposure characteristics through propensity score fine-stratification weighting. All analyses of initiator and switcher cohorts were conducted separately and then combined using fixed effects.Results51 208 patients with a mean age of 76 years were included, with 16 193 in the ARNI group. Adjusted HRs comparing ARNI with RAS blockade alone were 0.92 (95% CI 0.84 to 1.00) among initiators and 0.79 (95% CI 0.74 to 0.85) among switchers, with a combined estimate of 0.84 (95% CI 0.80 to 0.89). Adjusted 1-year RMST difference (95% CI) was 4 days in the initiator cohort (−1 to 9) and 12 days (8 to 17) in the switcher cohort, resulting in a pooled estimate of 9 days (6 to 12) favouring ARNI.ConclusionARNI treatment was associated with lower risk of a composite effectiveness endpoint compared with RAS blockade alone in older adults with HFrEF.

scholarly journals Role of renin-angiotensin system in development of heart failure induced by myocardial infarction in rats

2007 ◽  
Vol 79 (2) ◽  
pp. 250-259 ◽  
Author(s):  
Daniel C. Trindade ◽  
Raquel C. Trindade ◽  
Michelle P. Marassi ◽  
Ornélia P.P.R. Martins ◽  
Ricardo H. Costa-e-Sousa ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Heart Failure ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
P Wave ◽  
Coronary Artery Ligation ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Functional Changes ◽  
Rat Hearts

We investigated the morphologic and functional changes of infarcted rat hearts under a paradigm of angiotensinconverting enzyme inhibition. Myocardial infarction was induced by left coronary artery ligation and a control group (SHAM) underwent sham-operation. Infarcted rats received normal drinking water with (CAP group) or without (INF group) captopril. Functional assessment was performed by electro (ECG) and echocardiogram (ECHO) just before and 21 days after surgery. The ECG of INF and CAP showed similar values and resembled healed infarct after surgery. The most outstanding differences between INF and CAP were the prevention of the increase of P-wave and attenuation both in rightward deviation of the QRS axis and Q-wave amplitude in CAP compared with INF. The ECHO showed that captopril treatment improved the diastolic filling more than systolic performance. Cardiac dilatation and left congestive heart failure were observed only in INF. Both infarcted groups showed a scar tissue in the left ventricular wall, but the INF showed a higher scar area than CAP (49.7 ± 5.24 vs. 22.33 ± 6.19 respectively). These data suggest that the renin-angiotensin system induces morphologic and functional changes in post-infarcted rat hearts and which can be assessed by non-invasive exams.

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