imidapril and Cardiac-Output--Low

Angiotensin-converting enzyme (ACE) inhibitors improve the prognosis in mild, moderate and severe heart failure, as well as preventing the onset of heart failure in patients with chronic asymptomatic left-ventricular dysfunction and in those with reduced ejection fraction after myocardial infarction (MI). Imidapril is a long-acting ACE inhibitor that is rapidly converted in the liver to its active metabolite, imidaprilat. Maximum plasma concentrations of imidapril and imidaprilat are achieved after 2 and 5-6 hours, respectively, with corresponding elimination half-lives of 1.1-2.5 and 10-19 hours. Imidapril is used in the treatment of hypertension, chronic heart failure, acute MI and diabetic nephropathy. In patients with mild-to-moderate chronic heart failure, imidapril 10 mg once-daily increased exercise time and physical working capacity, decreased plasma atrial natriuretic peptide and brain natriuretic peptide levels and reduced blood pressure. It also improved left ventricular ejection fraction, being significantly more effective than bisoprolol, in patients with acute MI. Imidapril is well tolerated and preliminary studies suggest it has an advantage over captopril and enalapril in terms of a lower incidence of cough. In conclusion, imidapril is a well-investigated versatile ACE inhibitor for the treatment of a range of cardiovascular diseases.

Topics: Angiotensin-Converting Enzyme Inhibitors; Cardiac Output, Low; Drug Resistance; Drug-Related Side Effects and Adverse Reactions; Humans; Imidazolidines; Polymorphism, Genetic

We investigated the effect of adding spironolactone to treatment with an angiotensin-converting enzyme (ACE) inhibitor, imidapril, in Dahl salt-sensitive (DS) hypertensive heart failure rats with preserved systolic function. Male DS rats were fed laboratory chow containing 8% NaCl from 7 weeks of age. Rats were divided into four groups and treated for 9 weeks with vehicle alone (water; n = 23), the ACE inhibitor imidapril (1 mg kg(-1) day(-1); n = 16), spironolactone (2 mg kg(-1) day(-1); n = 15), or a combination of imidapril and spironolactone at the doses above (n = 16). The left ventricular weight to body weight (BW) ratio was significantly lower in the imidapril group (3.28 +/- 0.30 mg g(-1)) and the combination group (3.34 +/- 0.38 mg g(-1)) than in the vehicle group (3.71 +/- 0.46 mg g(-1)). Adding spironolactone to imidapril inhibited an increase in the ratio of lung weight to BW (4.38 +/- 0.50 mg g(-1)) related to high salt intake, while monotherapy (imidapril group, 4.61 +/- 0.90 mg g(-1); spironolactone group, 5.40 +/- 2.50) did not significantly change the ratio from that seen with vehicle treatment (6.32 +/- 3.62 mg g(-1)). All active treatments (imidapril, 0.66% +/- 0.67%; spironolactone, 0.51% +/- 0.55%; both together, 0.31% +/- 0.26%) inhibited a salt-intake related increase in the percentage area representing fibrous tissue compared with vehicle treatment alone (1.81% +/- 1.51%). These findings suggest that adding spironolactone to an ACE inhibitor is more effective in improving pulmonary congestion and edema in hypertensive heart failure with preserved systolic function than an ACE inhibitor alone.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiac Output, Low; Drug Therapy, Combination; Hypertension; Imidazolidines; Male; Mineralocorticoid Receptor Antagonists; Pulmonary Edema; Rats; Rats, Inbred Dahl; Spironolactone

The renin-angiotensin system and endothelin are important regulators of the cardiovascular system. Although increased production of endothelin-1 (ET-1) is reported in patients with heart failure, the detailed mechanism remains to be determined. To elucidate the relationship between the renin-angiotensin system and ET-1 in hypertensive heart failure, we evaluated the effects of long-term treatment with imidapril, an angiotensin converting enzyme (ACE) inhibitor, on preproET-1, endothelin A receptor (ETAR), and ACE mRNA expression in the left ventricle and evaluated these in relation to myocardial remodeling in the failing heart of Dahl salt-sensitive (DS) hypertensive rats fed a high salt diet. In DS rats fed an 8% NaCl diet after the age of 6 weeks, a stage of concentric left ventricular hypertrophy at 11 weeks (DSLVH) was followed by a distinct stage of left ventricular failure with chamber dilatation at 18 weeks (DSHF). Imidapril (DSHF-IM, n = 8, 1 mg/kg/day, subdepressor dose) or vehicle (DSHF-V, n = 8) was given from stage DSLVH to DSHF for 7 weeks, and age-matched (18 weeks) Dahl salt-resistant rats fed the same diet served as the control group (DR-C, n = 8). In both groups, blood pressure was similar and significantly higher than in DR-C. Markedly increased left ventricular end-diastolic diameter and reduced fractional shortening in DSHF-V was significantly ameliorated in DSHF-IM using transthoracic echocardiography. The preproET-1, ETAR, and ACE mRNA levels in the left ventricle were significantly increased in DSHF-V compared with DR-C, and significantly suppressed in DSHF-IM compared with DSHF-V. DSHF-V demonstrated a significant increase in the wall-to-lumen ratio and perivascular fibrosis in coronary arterioles, and myocardial fibrosis, with all these parameters being significantly improved by imidapril. In conclusion, myocardial remodeling and heart failure in DS rats fed a high salt diet were significantly ameliorated by a subdepressor dose of imidapril, which may be attributable to a decrease in ET-1 mRNA expression and angiotensin II in the left ventricle.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Body Weight; Cardiac Output, Low; Endothelin-1; Endothelins; Gene Expression; Heart Ventricles; Hemodynamics; Hypertension; Imidazoles; Imidazolidines; Male; Myocardial Contraction; Myocardium; Organ Size; Peptidyl-Dipeptidase A; Protein Precursors; Rats; Rats, Inbred Dahl; Receptor, Endothelin A; Receptors, Endothelin; RNA, Messenger; Ventricular Remodeling