Combined Angiotensin II Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Further Attenuates Postinfarction Left Ventricular Remodeling

Mankad, Sunil; d’Amato, Thomas A.; Reichek, Nathaniel; McGregor, Walter; Lin, Jeff; Singh, Deepak; Rogers, W. Todd; Kramer, Christopher M.

doi:10.1161/01.cir.103.23.2845

Cited by 48 publications

(22 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous experimental and clinical studies reported additional benefits of the combination therapy in systolic heart failure as compared with the monotherapy with ACEI. 9,[25][26][27] The current study expanded those previous studies by demonstrating that this concept can be applied to DHF as well as systolic heart failure. Kim et al showed that the combination achieved more preventive benefits than a monotherapy in the same hypertensive DHF model when the medications were initiated before the appearance of hypertension, ventricular structural abnormalities, and diastolic dysfunction.…”

Section: Discussionsupporting

confidence: 65%

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

et al. 2004

View full text Add to dashboard Cite

Abstract-Diastolic heart failure (DHF) has become a social burden; however, evidences leading to its therapeutic strategy are lacking. This study investigated effects of addition of angiotensin II type 1 receptor blocker (ARB) to angiotensin-converting enzyme inhibitor (ACEI) at advanced stage of DHF in hypertensive rats. Dahl salt-sensitive rats fed 8% NaCl diet from age 7 weeks served as DHF model, and those fed a normal chow served as control. The DHF model rats were arbitrarily assigned to 3 treatment regimens at age 17 weeks: ACEI (temocapril 0.4 mg/kg per day), combination of ACEI (temocapril 0.2 mg/kg per day) with ARB (olmesartan 0.3 mg/kg per day), or placebo. At age 17 weeks, this model represents progressive ventricular hypertrophy and fibrosis, relaxation abnormality, and myocardial stiffening. Data were collected at age 20 weeks. As compared with the monotherapy with ACEI, the addition of ARB induced more prominent suppression of ventricular hypertrophy and fibrosis, leading to suppression of myocardial stiffening, improvement of relaxation, and inhibition of hemodynamic deterioration. Such benefits were associated with greater decreases in reactive oxygen species ( Key Words: diastole Ⅲ angiotensin II Ⅲ angiotensin-converting enzyme Ⅲ heart failure Ⅲ oxidative stress O ccurrence of congestive heart failure despite preserved ejection fraction is attributed to left ventricular (LV) diastolic dysfunction and is termed diastolic heart failure (DHF). It consists of a high proportion of patients with congestive heart failure, and its major underlying cardiovascular disease is a hypertensive heart disease. 1,2 Despite the social burden of DHF, its therapeutic strategy has not been established.We have demonstrated that Dahl-Iwai salt-sensitive rats fed 8% NaCl from age 7 weeks present hypertension followed by compensatory LV hypertrophy with LV relaxation abnormality at approximately age 13 weeks; further progression of LV hypertrophy and development of LV fibrosis with LV relaxation abnormality and myocardial stiffening at approximately age 17 weeks; and overt DHF with increased LV filling pressure and pulmonary congestion at approximately age 20 weeks. 3,4 Using this model, our and other experimental studies demonstrated preventive effects of angiotensin II type 1 receptor blocker (ARB), angiotensin-converting enzyme inhibitor (ACEI), and their combination when initiated before the onset of LV diastolic dysfunction (at age 7 or 8 weeks). 5,6 However, therapeutic effects of any medication in DHF remain to be clarified when initiated at an advanced stage with LV diastolic dysfunction and structural alterations.A few retrospective studies demonstrated better prognosis in association with the prescription of ACEI in patients with DHF. 7,8 Recent clinical trials showed benefits of an addition of ARB to ACEI in patients with systolic heart failure. 9,10 The Candesartan in Heart Failure: Assessment of Reduction in Mortality and Morbidity (CHARM)-Preserved trial reported that ARB reduced hospitalization for wors...

show abstract

Section: Discussionsupporting

confidence: 65%

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

et al. 2004

View full text Add to dashboard Cite

show abstract

“…22 By contrast, other studies report that ACE inhibition and AT 1 receptor antagonism provide similar improvement of endothelial dysfunction. 7,21,23 Our results suggest that ACE inhibition may offer greater benefits, because ACEi lower tissue Ang II levels and increase tissue bradykinin levels, which causes NO to increase, whereas AT 1 receptor antagonists may only block the AT 1 receptor. However, whether it is more beneficial to use both ACEi and AT 1 receptor antagonists than either inhibitor alone still awaits the outcome of several ongoing clinical trials.…”

Section: Discussionmentioning

confidence: 80%

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

2002

View full text Add to dashboard Cite

Abstract-Angiotensin-converting enzyme inhibitors (ACEi) reduce cardiovascular morbidity and mortality by improving coronary perfusion, reducing ventricular hypertrophy and remodeling, and preventing progression of coronary atherosclerosis. However, the cellular mechanisms underlying the beneficial effects of ACEi are not fully understood. We studied the in vivo effects of ACE inhibition with perindopril on cellular expression of ACE, AT 1 receptors and 2 nitric oxide synthase (NOS) isoforms, endothelial (eNOS) and inducible NOS (iNOS), in human blood vessels using quantitative in vitro autoradiography and immunocytochemistry. Seven patients with ischemic heart disease were treated with perindopril (4 mg/d) for up to 5 weeks before elective coronary bypass surgery, whereas controls did not receive the ACEi (nϭ7). Perindopril decreased plasma ACE by 70% and the plasma angiotensin II to angiotensin I ratio by 57% and reduced vascular ACE to approximately 65% of control levels in both endothelium and adventitia. By contrast, AT 1 receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients. Both eNOS and iNOS expression seemed to increase during perindopril treatment. These results suggest that suppression of angiotensin II formation in the vascular wall and increased expression of eNOS and iNOS during ACE inhibition may be beneficial in reversing endothelial dysfunction in patients with cardiovascular disease. Because vascular AT 1 receptor expression is increased during chronic ACE inhibition, more clinical studies are required to determine whether it is necessary to combine ACE inhibitors and AT 1 receptor antagonists in clinical management of heart failure, coronary heart disease, and hypertension (Hypertension. 2002;39[part 2]:634-638.)

show abstract

“…In hemodialysis patients, one retrospective study demonstrated a 52% reduction in mortality risk in unselected patients who were treated with ACEI, which was independent of antihypertensive effects (9). ACEI have pleiotropic cardiovascular effects, including reducing myocyte response to the intracardiac renin-angiotensin system (34), attenuating ventricular remodeling (35), and limiting sympathetic nervous activity (36). We speculate that these responses explain why ACEI/ARB therapy at the time of the CA was associated with a beneficial survival response in this study.…”

Section: Factors That Influence Survival After Camentioning

confidence: 99%

Predictors of Survival after Cardiac Arrest in Outpatient Hemodialysis Clinics

Pun

Lehrich

Smith

et al. 2007

Clinical Journal of the American Society of Nephrology

109

View full text Add to dashboard Cite

Combined Angiotensin II Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Further Attenuates Postinfarction Left Ventricular Remodeling

Cited by 48 publications

References 47 publications

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Predictors of Survival after Cardiac Arrest in Outpatient Hemodialysis Clinics

Contact Info

Product

Resources

About

Combined Angiotensin II Receptor Antagonism and Angiotensin-Converting Enzyme Inhibition Further Attenuates Postinfarction Left Ventricular Remodeling

Cited by 48 publications

References 47 publications

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

AT1 Receptor Blocker Added to ACE Inhibitor Provides Benefits at Advanced Stage of Hypertensive Diastolic Heart Failure

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT 1 Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease

Predictors of Survival after Cardiac Arrest in Outpatient Hemodialysis Clinics

Contact Info

Product

Resources

About

Perindopril Alters Vascular Angiotensin-Converting Enzyme, AT ₁ Receptor, and Nitric Oxide Synthase Expression in Patients With Coronary Heart Disease