Disease relevance of DU 1219

• These results demonstrated that alacepril was effective in essential hypertension both at rest and during exercise, suggesting that the antihypertensive effect during exercise might be related to the decrease in pressor hormones, especially in plasma angiotensin II [1].
• Ten uncomplicated essential hypertensive patients with left ventricular hypertrophy, aged 53 +/- 8 years, were treated with alacepril alone for 12 months [2].
• In conclusion, a single oral administration of the ACE inhibitor alacepril (50mg) elicited beneficial effects against exercise-induced myocardial ischemia in patients with stable effort angina during chronic nitrate treatment [3].
• Effects of the angiotensin converting enzyme inhibitors captopril, rentiapril, and alacepril in patients with essential and renovascular hypertension [4].
• Administration of alacepril did not cause tachycardia in response to the decrease in blood pressure [5].

Psychiatry related information on DU 1219

• However, alacepril at the same dose did not affect the general behavior, convulsions induced by maximal electroshock, pentetrazol and strychnine, active avoidance in mice and body temperature in rats [6].

High impact information on DU 1219

• CONCLUSIONS: Both amlodipine and alacepril decreased blood pressure and urinary protein, and ameliorated the renal injury induced by the HC diet in rats [7].
• DESIGN AND METHODS: Male Sprague-Dawley rats were given either an HC diet only (n = 5), an HC diet and amlodipine (n = 10) or an HC diet and alacepril (n = 10) [7].
• The response of the renal eicosanoid system to alacepril was inadequate, but cyclic GMP excretion, an indicator of nitric oxide formation, was significantly enhanced and lipid peroxidation in the kidney was decreased [8].
• PURPOSE: In this work, the alacepril thiolesterase, which catalyzes the hydrolyzing reaction of the thiolester linkage in alacepril and the conversion from alacepril to deacetylalacepril, was purified from rat liver cytosol and characterized [9].
• Plasma renin activity was significantly increased (p<0.05) after administration of alacepril, indicating that alacepril significantly blocked ACE activity in our patients [3].

Chemical compound and disease context of DU 1219

• The maximal hypotension was observed 1 and 5 h after administration of captopril and alacepril, respectively [10].
• The ACE inhibitor alacepril suppresses atherogenesis independent of serum lipids in cholesterol-fed rabbits--critical analysis with new ultrasound technique [11].
• Alacepril at the high oral dose of 600 mg/kg prolonged the hexobarbital sleeping time and potentiated the reserpine-induced hypothermia in mice [6].

Biological context of DU 1219

• RESULTS: Alacepril decreased systolic blood pressure (SBP) [8].
• Alacepril significantly lowered mean blood pressure at rest and at the same exercise load as before treatment without affecting heart rate response [1].
• The tilt and arterial baroreflex tests were repeated 12 weeks after alacepril treatment (50 mg x day(-1)) [12].
• The aim of this study was to elucidate the effects of antihypertensive treatment with alacepril on insulin resistance in these diabetic SHR [13].
• Renal plasma flow (RPF) and glomerular filtration rate (GFR) were examined before and after 12-week administration of alacepril, by [131I]hippuran and [99mTc]DTPA, respectively [14].

Anatomical context of DU 1219

• Alacepril, an ACE inhibitor with SH-group, inhibited the oxygen radical production and generation by lung alveolar macrophages harvested from both rats and guinea pigs in a dose-dependent fashion [15].
• Angiotensin-converting enzyme (ACE) activity in the thoracic aorta in the high-cholesterol-diet group was significantly higher than that in the normal-diet group, and the ACE activities in the alacepril groups were lower than that in the high-cholesterol-diet group [16].
• These results suggest that alacepril works as anti-atherogenic agent through inhibiting endothelial-dependent adhesive interactions with monocytes induced by 7-KC and TNF-alpha [17].
• Antihypertensive mechanism of alacepril. Effects of its metabolites on the peripheral sympathetic nervous system [18].
• Alacepril at the oral dose of 60 mg/kg decreased the total acidity in pylorus ligated rats, and at higher doses depressed the intestinal charcoal meal passage in mice [19].

Associations of DU 1219 with other chemical compounds

• ACE inhibitors with and without an SH-group (alacepril and lisinopril, respectively) were tested for their effect on oxygen radical formation by BAL cells; both ACE inhibitors inhibited oxygen radical production and generation by BAL cells from both young and aged guinea pigs in a dose-dependent manner [20].
• The end-systolic wall stress/left ventricular end-systolic volume index, as an index of left ventricular contractility, was decreased significantly after treatment with nicardipine SR but was not changed after treatment with alacepril [21].
• Angiotensin converting-enzyme inhibitors (alacepril and imidapril) or an AT1-receptor antagonist (SC-52458) was administered to 10-week-old spontaneously hypertensive rats (SHR) for 7 days, and cardiac mRNA levels for contractile proteins and atrial natriuretic polypeptide (ANP) were comprehensively measured [22].
• Furthermore, the direct comparison of alacepril and captopril was attempted by the difference in blood pressures and in ACE inhibitions induced after oral administration of the agents [10].
• Antihypertensive mechanism of alacepril: effect on norepinephrine-induced vasoconstrictive response in vitro and in vivo [23].

Gene context of DU 1219

• Alacepril inhibited the production of ROS in HAECs stimulated by 7-KC or TNF-alpha [17].
• Antihypertensive activity of alacepril, an orally active angiotensin converting enzyme inhibitor, in renal hypertensive rats and dogs [24].
• These results indicate that the antihypertensive activity of alacepril is due to the suppression of renin-angiotensin-aldosterone system and the enhancement of kallikrein-kinin-prostaglandin system through the inhibition of ACE (kininase II) activity in vivo [25].
• Alacepril (1-[(S)-3-acetylthio-2-methylpropanoyl]-L-prolyl-L-phenylalanine, DU-1219) showed a dose related and long lasting antihypertensive effect in renal hypertensive rats (two-kidney, one-clip), a typical renin dependent hypertensive model [24].
• Alacepril, an ACE inhibitor bearing SH-group, inhibited the oxygen radical production and generation by BAL cells from COPD patients in a dose-dependent fashion [26].

Analytical, diagnostic and therapeutic context of DU 1219

• After this period, efficacy of single oral administration of either alacepril (50 mg) or its placebo on exercise-induced angina and electrocardiographic changes was examined by treadmill exercise test in a double-blind crossover design [3].
• Alacepril did not significantly alter the rate-pressure product, a marker of myocardial oxygen demand, during exercise test compared with placebo [3].
• The thiolesterase activity was assayed for alacepril as a substrate and the reaction product, deacetylalacepril, was measured using high-performance liquid chromatography [9].
• There were no significant differences in pulse pressure before and after treatment with trichlormethiazide, nicardipine and alacepril [27].
• Left ventricular mass, as estimated by echocardiography, was significantly decreased by alacepril treatment, although electrocardiographic and chest x-ray findings were not significantly altered [28].

References