benazepril and Cardiomegaly

The aim of this study was to compare the cardioprotective effects of salvianolic acid B (Sal B) and the angiotension-converting enzyme inhibitor, benazepril, in rats with chronic myocardial infarction (MI) that resulted from a coronary artery ligation for 4 weeks. The rats were divided into four groups: those undergoing a sham operation; a MI group; a MI+SalB group (100 mg/kg by a gavage, once a day for 4 weeks); a MI+benazepril group (10 mg/kg by a gavage, once a day for 4 weeks). The following parameters were measured: echocardiographic, hemodynamic and hemorheological changes, angiogenesis, infarct size and cardiac remodeling and the messenger ribonucleic acid (mRNA) of vascular endothelium growth factor (VEGF). Rats treated with SalB or benazepril manifested the following: (1) marked improvements in echocardiographic, hemodynamic and hemorheological parameters; (2) significant reduction of infarct size; (3) significantly attenuated heart, kidney and lung hypertrophies, left ventricular (LV) dilatation and fibrosis. The unique effects of SalB were angiogenesis and augmented VEGF expression in the border and remote noninfarcted left ventricular area. These results suggest that both SalB and benazepril exerted beneficial cardioprotective effects in our experimental system, but that the modality of Sal B was different from that of benazepril. The additional beneficial effects of Sal B relative to benazpril, augmenting VEGF expression and promoting angiogenesis, may result in improved myocardial microcirculation.

Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antioxidants; Benzazepines; Benzofurans; Blood Viscosity; Cardiomegaly; Chronic Disease; Collagen; Electrocardiography; Hemodynamics; Immunohistochemistry; Male; Myocardial Infarction; Myocardium; Neovascularization, Pathologic; Protective Agents; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Vascular Endothelial Growth Factor A; Ventricular Remodeling

The effects of chronic treatment with losartan, an angiotensin II type 1 (AT1) receptor antagonist, and benazepril, an angiotensin converting enzyme (ACE) inhibitor, on target-organ damage and abnormal circadian blood pressure (BP) rhythm were compared in stroke-prone spontaneously hypertensive rats (SHRSP). Losartan and benazepril were given by intraperitoneal infusion for 3 weeks after 17 weeks of age to minimize any influence of their different pharmacokinetic properties. BP was continuously monitored by telemetrical method before treatment and at the end of the observation period. The left ventricular (LV) weight, 24-hour urinary albumin excretion (UalbV) and morphological changes in the kidney were observed. Losartan and benazepril (1, 3 and 10 mg/day) reduced BP and LV weight in a dose-dependent manner with good correlation between the effects. Losartan significantly improved UalbV in a dose-dependent manner, whereas benazepril was effective at only 10 mg/day. Renal morphological analysis showed that reduction of glomerulosclerosis and collagen fiber thickness was related to the effect on UalbV, but not to the antihypertensive effects. Losartan improved the shifted circadian BP rhythm towards the active phase in a dose-dependent manner, whereas the improvement caused by 1 and 3 mg/day of benazepril was less effective than the same dosage of losartan. These results suggest that both losartan and benazepril can reduce cardiac hypertrophy showing good correlation with their antihypertensive effects, but losartan, especially at a low dose, alleviates renal damage more effectively than benazepril, with its effect correlating well with improvement of the abnormal circadian BP rhythm in SHRSP. Thus, the protective effect against hypertensive target organ damage of the AT1 receptor antagonist seems to be more effective than that of ACE inhibitor.

Topics: Aldosterone; Animals; Antihypertensive Agents; Benzazepines; Blood Pressure; Cardiomegaly; Circadian Rhythm; Collagen; Heart Rate; Hypertension; Kidney; Losartan; Male; Organ Size; Rats; Rats, Inbred SHR; Renin; Urine

We investigated the long-term effects of benazepril, a new non-sulfydryl angiotensin converting enzyme inhibitor, on ambulatory blood pressure (BP) and left ventricular (LV) anatomy and function in 13 never treated hypertensive patients (mean age 55 years--SD 9). Non-invasive ambulatory BP monitoring (Spacelabs 90202, a reading every 15 min for 24 hours) and standard and pulsed Doppler echocardiography were performed basally and after 12 months of therapy. Echocardiography was performed also at the end of 18th month of treatment. Eleven patients required a single daily dose of benazepril 10 (n = 9) or 20 (n = 2) mg, and two patients of 20 mg plus chlorthalidone 25 mg, to achieve clinical BP control. Average 24 h systolic/diastolic BP was 156/100 mmHg (SD 17/5) basally and 144/90 mmHg (SD 16/7) at the end of the 12th month of treatment (all p less than 0.01), LV mass index was 133 g/m2 basally and 113 g/m2 at the 12th month (p less than 0.01), early transmitral flow velocity (peak E) was 0.43 m/s (SD 0.11) basally and 0.62 (SD 0.13) m/s at the 12th month (p less than 0.01), and late transmitral flow velocity (peak A) did not change [0.67 (SD 0.10) m/s basally and 0.64 (SD 0.11) m/s at the 12th month]. Peak A/peak E ratio decreased from 1.69 (SD 0.57) to 1.31 (SD 0.37) (p less than 0.01). Peak aortic velocity, aortic acceleration time and aortic acceleration did not change. The per cent reduction of LV mass index was more closely related to the reduction of average 24 h systolic (r = 0.66, p = 0.013) and diastolic (r = 0.72, p = 0.005) BP than to the reduction of casual systolic (r = 0.37, p = NS) and diastolic (r = 0.42, p = NS) BP. None of the echocardiographic indices changed between the 12th and 18th month of treatment. In a control group of 13 age- and sex-matched healthy normotensive volunteers who underwent 24 h ambulatory BP monitoring and echocardiography twice, 12 months apart, there were no statistically significant BP or echographic changes. In summary, long-term antihypertensive treatment with benazepril provided and effective 24 h BP control, associated with regression of LV hypertrophy and improvement in LV diastolic filling, without changes in LV systolic function.

Topics: Ambulatory Care; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Benzazepines; Blood Pressure; Blood Pressure Determination; Cardiomegaly; Echocardiography, Doppler; Female; Follow-Up Studies; Humans; Hypertension; Male; Middle Aged; Monitoring, Physiologic

To study the effects of a novel angiotensin I converting enzyme inhibitor (ACEI) on hypertension-induced cardiac hypertrophy, benazepril hydrochloride (CGS 14824 A, CAS 86541-74-4) at the dose of 3 and 10 mg/kg/d p.o. was administered to spontaneously hypertensive rats from 4 to 16 weeks of age. In addition to suppression of developing blood pressure, benazepril hydrochloride reduced both the wet weights of whole heart and left ventricle dose-dependently and significantly. Benazepril hydrochloride had no effect on hydroxyproline concentration and content or protein concentration in the left ventricle, whereas is reduced the total protein content dose-dependently. Serum ACE activity was significantly reduced at 10 mg/kg/d of benazepril hydrochloride, but renin activity, aldosterone and noradrenaline concentration in serum were not changed. From the microscopic findings of the left ventricle, benazepril hydrochloride reduced the myocardial hypertrophy significantly. From these results, benazepril hydrochloride seems to suppress the increase in volume load by acting through the renin-angiotensin-aldosterone system, and dose not seem to cause a significant reflex of catecholamine which often occurs with peripheral vessels dilation. Thus, benazepril hydrochloride may be expected to suppress cardiac hypertrophy in patients with hypertension.

Topics: Aldosterone; Angiotensin-Converting Enzyme Inhibitors; Animals; Benzazepines; Biomarkers; Blood Pressure; Cardiomegaly; Heart Rate; Hydroxyproline; Hypertension; Male; Muscle Proteins; Myocardium; Norepinephrine; Organ Size; Rats; Rats, Inbred SHR; Renin