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Mol Cell Biochem. 1995 Jun 7-21;147(1-2):51-5.
Ventricular remodeling: insights from pharmacologic interventions with angiotensin-converting enzyme inhibitors.

Goldstein S, Sharov VG, Cook JM, Sabbah HN.

Department of Medicine, Henry Ford Heart and Vascular Institute, Detroit, Michigan, USA.

Structural remodeling of the left ventricular (LV) myocardium develops in a time-dependent fashion following acute myocardial infarction and may be an integral component in the transition toward overt heart failure. Globally, the remodeling process is characterized by progressive LV enlargement and increased chamber sphericity. At the cellular level, the remodeling process is associated with myocyte slippage, hypertrophy, and accumulation of collagen in the interstitial compartment. In the present study, we examined the effects of early, long-term monotherapy with the angiotensin converting enzyme (ACE) inhibitor, enalapril, on the progression of LV remodeling in dogs with LV dysfunction (ejection fractions 30-40%) produced by multiple sequential intracoronary microembolizations. Dogs were randomized to 3 months oral therapy with enalapril (n = 7) or to no treatment (n = 7). In untreated dogs, LV end-systolic volume index (ESVI), end-diastolic volume index (EDVI) and chamber sphericity increased significantly during the 3 months follow-up period. In contrast, in dogs treated with enalapril ESVI, EDVI and chamber sphericity remained essentially unchanged. Treatment with enalapril attenuated myocyte hypertrophy and the accumulation of interstitial collagen in comparison to untreated dogs. These data indicate that early treatment with ACE inhibitors can prevent the progression of LV remodeling in dogs with LV dysfunction. Afterload reduction, inhibition of direct action of angiotensin-II and possibly the decrease in bradykinin degradation elicited by ACE inhibition may act in concert in preventing the progression LV chamber remodeling.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=7494555&dopt=Abstract




Ann Intern Med. 1987 Mar;106(3):346-54.
Functional renal insufficiency during long-term therapy with captopril and enalapril in severe chronic heart failure.

Packer M, Lee WH, Medina N, Yushak M, Kessler PD.

Renal function was evaluated in 104 patients with severe chronic heart failure whom we treated with captopril or enalapril. Seventy patients showed no change or an improvement in renal function (group A), and 34 patients developed functional renal insufficiency (group B). Before converting-enzyme inhibition, group B patients received higher doses of furosemide (p less than 0.02) and had lower central venous pressures (p less than 0.05) than group A patients. After 1 to 3 months of converting-enzyme inhibition, an excessive reduction in left ventricular filling pressure (to less than 15 mm Hg) or mean arterial pressure (to less than 60 mm Hg) was noted in 28 of 34 (82%) patients in group B but in only 22 of 70 patients in group A (31%) (p less than 0.001). At the end of the study, drug-induced azotemia resolved after a reduction in the dosage of diuretics, despite unaltered treatment with captopril and enalapril. Hence, the deterioration of renal function after converting-enzyme inhibition in heart failure is not a toxic or immunologic reaction to therapy but results from specific hemodynamic events that can be ameliorated by sodium repletion.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3028221&dopt=Abstract




Diabetes Care. 1987 Mar-Apr;10(2):200-4.
Effects of enalapril in insulin-dependent diabetic subjects with mild to moderate uncomplicated hypertension.

Passa P, LeBlanc H, Marre M.

The antihypertensive efficacy of enalapril and its effects on the metabolism and kidney function were investigated in 11 insulin-dependent diabetic subjects with uncomplicated mild to moderate hypertension. During a short-term single-blind controlled trial, one daily dose of 20 or 40 mg enalapril significantly reduced both systolic and diastolic blood pressure. In the supine position, mean systolic blood pressure declined from 169 +/- 6 to 142 +/- 6 mmHg (P less than .01) and mean diastolic blood pressure from 101 +/- 1.5 to 85 +/- 2 mmHg (P less than .001). No changes in heart rate or postural hypotension were observed. During 1 yr of treatment, the antihypertensive efficacy of enalapril did not decline, and no clinical side effects were observed. Inhibition by enalapril of angiotensin-converting enzyme did not modify daily insulin requirements, glycemic control, uricemia, or lipid metabolism; kalemia and the markers of diabetic nephropathy were not significantly altered. These results suggest that enalapril once daily should be used as the first step in the treatment of diabetic patients with mild to moderate hypertension.

online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=3034532&dopt=Abstract













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