enalapril and Hypertrophy--Right-Ventricular

To compare the effects of candesartan cilexetil and enalapril maleate on right ventricular myocardial remodeling in dogs with experimentally induced pulmonary stenosis.. 24 Beagles.. 18 dogs underwent pulmonary arterial banding (PAB) to induce right ventricular pressure overload, and 6 healthy dogs underwent sham operations (thoracotomy only [sham-operated group]). Dogs that underwent PAB were allocated to receive 1 of 3 treatments (6 dogs/group): candesartan (1 mg/kg, PO, q 24 h [PABC group]), enalapril (0.5 mg/kg, PO, q 24 h [PABE group]), or no treatment (PABNT group). Administration of treatments was commenced the day prior to surgery; control dogs received no cardiac medications. Sixty days after surgery, right ventricular wall thickness was assessed echocardiographically and plasma renin activity, angiotensin-converting enzyme activity, and angiotensin I and II concentrations were assessed; all dogs were euthanatized, and collagenous fiber area, cardiomyocyte diameter, and tissue angiotensin-converting enzyme and chymase-like activities in the right ventricle were evaluated.. After 60 days of treatment, right ventricular wall thickness, cardiomyocyte diameter, and collagenous fiber area in the PABNT and PABE groups were significantly increased, compared with values in the PABC and sham-operated groups. Chymase-like activity was markedly greater in the PABE group than in other groups.. Results indicated that treatment with candesartan but not enalapril effectively prevented myocardial remodeling in dogs with experimentally induced subacute right ventricular pressure overload.

Topics: Animals; Antihypertensive Agents; Benzimidazoles; Biphenyl Compounds; Constriction, Pathologic; Dog Diseases; Dogs; Enalapril; Heart Ventricles; Hypertrophy, Right Ventricular; Pulmonary Valve Stenosis; Tetrazoles; Ventricular Remodeling

The effect of enalapril in combination with bronchodilators, diuretics, antibiotics and/or steroids, was compared with that of conventional treatment with diuretics, steroids and antibiotics alone in 30 patients of chronic cor-pulmonale. The effect was studied on right ventricular dimensions and renal profile after a period of 6 weeks treatment. The control patients showed a significant decrease of RVIDED and increase in GFR, but the decrease of RVAWT and increase of 'a' wave amplitude was insignificant. However when the ACE-inhibitor enalapril was added to the treatment, there was a significant decrease of RVIDED, RVAWT and an increase of 'a' wave amplitude with a significant improvement in the GFR. A comparison between both the groups showed that the increase of GFR and decrease of RVIDED was higher in enalapril group than controls. The increase of 'a' wave amplitude was also greater in enalapril group. Thus enalapril appears to be of value in chronic cor-pulmonale, where it decreases pulmonary hypertension and thus right ventricular after load. It also decreases renal vascular resistance increasing the renal blood flow, thus improving the GFR.

Topics: Adult; Aged; Angiotensin-Converting Enzyme Inhibitors; Anti-Bacterial Agents; Bronchodilator Agents; Diuretics; Drug Therapy, Combination; Enalapril; Female; Glomerular Filtration Rate; Humans; Hypertrophy, Right Ventricular; Male; Middle Aged; Pulmonary Heart Disease

Myocardial infarction is a major cause of cardiac dysfunction. All components of the cardiac renin-angiotensin system (RAS) are upregulated in myocardial infarction. Angiotensin-converting enzyme (ACE) and ACE2 are key enzymes involved in synthesis of components of RAS and provide a counter-regulatory mechanism within RAS. We compared the cardioprotective effect of the ACE2 activator diminazene aceturate (DIZE) versus the ACE inhibitor enalapril on post acute myocardial infarction (AMI) ventricular dysfunction in rats. Adult male rats received subcutaneous injections of either saline (control) or isoproterenol (85 mg/kg) to induce AMI. Rats with AMI confirmed biochemically and by ECG, were either left untreated (AMI) or administered DIZE (AMI + DIZE) or enalapril (AMI + enalapril) daily for 4 weeks. DIZE caused a significant activation of cardiac ACE2 compared with enalapril. DIZE caused a significantly greater enhancement of cardiac hemodynamics. DIZE also caused greater reductions in heart-type fatty acid binding protein (H-FABP), β-myosin heavy chain (β-MYH), and in heart mass to total body mass ratio. These results indicated that activation of cardiac ACE2 by DIZE enhanced the protective axis of RAS and improved myocardial function following AMI, whereas enalapril was not sufficient to restore all cardiac parameters back to normal.

Topics: Acute Disease; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiotonic Agents; Diminazene; Enalapril; Enzyme Activation; Heart Ventricles; Hypertrophy, Right Ventricular; Male; Myocardial Infarction; Peptidyl-Dipeptidase A; Rats; Rats, Wistar

The present study evaluated the importance of ovarian functions and the renin-angiotensin system in the progression of the right ventricular (RV) hypertrophy. Female Sprague-Dawley rats were bilaterally ovariectomized (Ovx) and injected with monocrotaline (MCT, 60 mg/kg, sc). Four weeks after MCT-treatment, only the male and Ovx female rats showed marked RV hypertrophy. The hypertrophied RV of the male-MCT and Ovx-MCT rats exhibited remarkably elevated renin mRNA levels. Gene expression levels of angiotensinogen, TGF-beta1, and endothelin-1 in the hypertrophied RV also increased, but to the less degree than did the renin mRNA. To investigate beneficial effects of estrogen or enalapril on progression of the pulmonary hypertension and RV hypertrophy, histological changes of the lung and heart were examined. Sham-MCT female rats showed histological changes indicating pulmonary hypertension without RV hypertrophy. In contrast, Ovx-MCT rats showed marked RV hypertrophy with pathological changes, denoting severe pulmonary and myocardial injuries. Estrogen-or enalapril-treated Ovx-MCT rats did not show RV hypertrophy, and showed remarkably ameliorated ultrastructural changes in the lung and RV. These results from this rat model suggest that both estrogen and inhibition of the renin-angiotensin system have protective functions against the development of the pulmonary hypertension and cardiac remodeling.

Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensinogen; Animals; Body Weight; Densitometry; Disease Progression; Enalapril; Endothelin-1; Estrogens; Female; Hypertrophy, Right Ventricular; Male; Microscopy, Electron; Monocrotaline; Ovariectomy; Rats; Rats, Sprague-Dawley; Renin; Reverse Transcriptase Polymerase Chain Reaction; RNA; RNA, Messenger; Sex Factors; Transforming Growth Factor beta; Transforming Growth Factor beta1; Ventricular Remodeling

Pulmonary arterial hypertension (PAH) is associated with structural changes in the pulmonary vasculature characterized by the proliferation of cellular components of the vessels. ACE inhibitor (ACEI) may have beneficial effects in treating PAH, but its precise mechanism of action in the remodeling process is unclear. p21 is a cyclin-dependent kinase inhibitor that may have a protective role in this process by inhibiting cellular proliferation. Endothelial nitric oxide synthase (eNOS) has also been shown to be protective by its vasodilatory effect. Therefore, we investigated whether expression of p21 and eNOS was modulated by ACEI treatment in a rat model.. Monocrotaline (MCT) was administered to 2 groups of Sprague-Dawley rats fed a high-cholesterol diet, ie, one group received MCT concomitantly with enalapril treatment (MCT(+)/ACEI(+) rats), and the other group did not receive enalapril (MCT(+)/ACEI(-) rats). After 5 weeks, MRI showed right ventricular hypertrophy in MCT(+)/ACEI(-) rats. MCT(+)/ACEI(+) rats showed a preserved right ventricular morphology. Isolated pulmonary perfusion studies showed that ACEI significantly upregulated NO production, as measured by nitrite levels. Addition of N-methyl-D-glucamine dithiocarbamate-Fe solution, an NO-trapping agent, reversed the basal vasodilatory effect of ACEI in the pulmonary vasculature. Immunoblot analysis showed decreased p21 and eNOS expression in the lung in MCT(+)/ACEI(-) rats, whereas their expression was preserved with enalapril treatment.. ACEI suppresses the development of MCT-induced PAH in rats. The mechanism of action might involve the preservation of p21 and eNOS expression. Both p21 and endothelium-derived NO appear to have protective roles in the development of PAH.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Blood Pressure; Cells, Cultured; Cyclin-Dependent Kinase Inhibitor p21; Cyclins; Dietary Fats; Disease Models, Animal; Enalapril; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; In Vitro Techniques; Lung; Magnetic Resonance Imaging; Male; Monocrotaline; Nitrates; Nitric Oxide Donors; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Nitrites; Perfusion; Pulmonary Artery; Rats; Rats, Sprague-Dawley; Signal Transduction

Chronic hypoxia induces pulmonary hypertension and right ventricular hypertrophy. These changes are completely reversible, except for persistent myocardial fibrosis. The aim of the present study was to determine whether treatment with the angiotensin-converting enzyme (ACE) inhibitor enalapril can reduce the ventricular collagen content in animals recovering from chronic hypoxia. Adult male Wistar rats were exposed to intermittent high-altitude hypoxia simulated in a barochamber (7000 m, 8 hr/day, 5 days a week, 24 exposures), then transferred to normoxia and divided into two groups: (a) treated with enalapril (0.1 g/kg/day for 60 days) and (b) without treatment. The corresponding control groups were kept under normoxic conditions. Enalapril significantly decreased the heart rate, systemic arterial pressure, and absolute left and right ventricular weights in both hypoxic and control rats; on the other hand, the pulmonary blood pressure was unchanged. The content and concentration of collagen was reduced in both ventricles of enalapril-treated hypoxic and control animals by 10-26% compared with the corresponding untreated groups. These data suggest that the partial regression of cardiac fibrosis due to enalapril may be independent of the pressure load.

Topics: Altitude Sickness; Angiotensin-Converting Enzyme Inhibitors; Animals; Body Weight; Chronic Disease; Collagen; Enalapril; Hemodynamics; Hydroxyproline; Hypertension, Pulmonary; Hypertrophy, Right Ventricular; Hypoxia; Male; Myocardium; Organ Size; Pulmonary Fibrosis; Rats; Rats, Wistar