Disease relevance of cilazapril

• Subacute cutaneous lupus erythematosus associated with cilazapril [1].
• In 12 patients with essential hypertension treated with 5 mg cilazapril, left ventricular mass was reduced by 30%, which was closely related to the change in mean arterial blood pressure [2].
• The effects of cilazapril were assessed in four experimental groups: normotensive rats, spontaneously hypertensive rats, hypertensive rats with a renal artery stenosis induced by clipping (two-kidney, one-clip rats), and hypertensive rats with uninephrectomy, high salt intake, and administration of deoxycorticosterone (DOCA) [3].
• METHODS: Rats were subjected to coronary artery ligation and 9 months of treatment with mibefradil (15 mg/kg body weight per day) or cilazapril (10 mg/kg per day) or no treatment [4].
• The increased glomerular pressure and the albuminuria were decreased by cilazapril but systemic pressure was not [5].

High impact information on cilazapril

• The role of a local angiotensin system in the vascular response to arterial injury was investigated by administering the angiotensin-converting enzyme (CE) inhibitor cilazapril to normotensive rats in which the left carotid artery was subjected to endothelial denudation and injury by balloon catheterization [6].
• Arterial JNK activation at 2 or 5 minutes was remarkably suppressed by E4177 (an angiotensin AT1 receptor antagonist) and cilazapril (an ACE inhibitor) [7].
• The increased AP-1 DNA binding activity was significantly inhibited by both E4177 and cilazapril [7].
• Treatment with the ACE inhibitor cilazapril lowered the blood pressure of L-NAME-treated rats equally whether or not they were receiving the ETA antagonist [8].
• Cilazapril, a converting enzyme inhibitor, has been shown to significantly decrease the extent of intimal smooth muscle cell proliferation after arterial injury in a normotensive rat model [9].

Chemical compound and disease context of cilazapril

• These data indicate that the angiotensin-converting enzyme inhibitor cilazapril specifically inhibits the proliferative response to balloon injury and that heparin and cilazapril inhibit intimal hyperplasia through different mechanisms [10].
• Three patients withdrew from cilazapril because of mild angioedema, headaches, and chest pain, respectively, and three patients withdrew from hydrochlorothiazide treatment because of fatigue, dizziness, and gastric hemorrhage [11].
• Captopril increased maximal coronary flow and decreased cardiac hypertrophy to the same level as cilazapril only at the highest dose [12].
• A multicenter, randomized double-blind study of 6 months' duration was performed in 540 patients (average age 54 years, 57% male) with mild-to-moderate essential hypertension to determine the relative effects on quality of life of cilazapril, atenolol, and nifedipine retard [13].
• Treatment of hypertension was begun at 3 months of age with cilazapril (45 mg/kg/day), an angiotensin converting enzyme (ACE) inhibitor, or with hydralazine (18 mg/kg/day) [14].

Biological context of cilazapril

• Cilazapril resulted in a significant decrease in mean arterial pressure and coronary vascular resistance, together with a prolonged increase in coronary sinus blood flow (CSBF) [15].
• Antihypertensive efficacy of cilazapril in general practice: assessment by ambulatory blood pressure monitoring [16].
• Clinical pharmacology of cilazapril [17].
• Cilazapril increased effective renal plasma flow slightly [17].
• Within three hours after oral administration of cilazapril, the time to peak filling rate of the left ventricle, expressed as a percentage of diastole, was reduced from 44.5 +/- 13.2 percent to 31.2 +/- 7.2 percent (p less than 0.05) [18].

Anatomical context of cilazapril

• To assess the influence of cilazapril on myofibrotic changes after balloon injury, control (n = 7) or cilazapril-treated (n = 9) (20 mg/kg b.i.d.) normal 3-month-old pigs underwent dilatation angioplasty of the right, and deendothelialization of the left common carotid artery [9].
• Restenosis, reocclusion and adverse cardiovascular events after successful balloon angioplasty of occluded versus nonoccluded coronary arteries. Results from the Multicenter American Research Trial With Cilazapril After Angioplasty to Prevent Transluminal Coronary Obstruction and Restenosis (MARCATOR) [19].
• The significant thickening of the basement membrane observed in the diabetic normotensive (132.8+/-19.4 nm) and diabetic hypertensive (150.3+/-20.2 nm) groups was decreased by cilazapril in the diabetic hypertensive group (116.7+/-11.0 nm, p<0.01), but was unaffected in the normotensive (131.9+/-17.3 nm) group [20].
• Candesartan and cilazapril equally prevented increases in hypertrophy in noninfarcted myocardium, left ventricular dilatation, and ejection fraction at 4 weeks [21].
• Brachial artery acetylcholine infusions increased forearm blood flow from 2.95 +/- 1.5 to a maximum of 22.8 +/- 11.5 ml.min-1.100 ml-1 forearm tissue and decreased forearm vascular resistance from 48.1 +/- 34.1 to 6.9 +/- 6.9 units before cilazapril [22].

Associations of cilazapril with other chemical compounds

• However, the degree of BP control, with both cilazapril and amlodipine, can successfully delay the slope of GFR decline in hypertensive NIDDM patients with or without incipient nephropathy [23].
• Blood pressure at entry was 158/103 mm Hg (cilazapril) and 160/103 mm Hg (hydrochlorothiazide) [11].
• Mibefradil decreased systolic blood pressure, although to a lesser extent than cilazapril [4].
• In study 2, 20 patients with EH received an oral glucose tolerance test and a euglycemic insulin clamp before and after 3 months of treatment with cilazapril [24].
• In clinical pharmacology studies cilazapril, after its bioactivation to cilazaprilat, was characterized as a potent, reversible angiotensin-converting enzyme (ACE) inhibitor with a terminal half-life of 30 to 50 hours consistent with saturable binding to ACE [17].

Gene context of cilazapril

• Accordingly, SHR were treated with an angiotensin converting enzyme inhibitor, cilazapril, in addition to the ETA receptor antagonist [25].
• OBJECTIVES: Expression of NHE-1 and NHE-3 isoforms and sodium pump activity (PNP), and their modulation by blood pressure (BP), PGE(2) and TXB(2) were examined in the kidneys of 2K-1C rats treated with cilazapril for short- (4 and 24 h) and long-term (7 days) periods [26].
• Moreover, the reduction of arterial blood pressure was similar to the action of the angiotensin converting enzyme inhibitor cilazapril and was not associated with reflex tachycardia in contrast to the pure vasodilator minoxidil [27].
• We also examined the effects of treatment with cilazapril, an angiotensin I-converting enzyme inhibitor (ACEI), and L-158,809, an AT1 receptor antagonist, on these expressions in DOCA-treated rats [28].
• Intravenous administration of cilazapril to anesthetized dogs resulted in a rise in plasma renin activity and a significant fall in plasma angiotensin II levels [29].

Analytical, diagnostic and therapeutic context of cilazapril

• After assessing the short-term effects and dose titration with cilazapril, a new long-acting ACE inhibitor, 21 patients were randomized to receive either placebo or the ACE inhibitor [30].
• However, recent clinical trials (MERCATOR and MARCATOR) reported that treatment with low (antihypertensive) doses of an ACE inhibitor (cilazapril) failed to prevent restenosis [31].
• Efficacy and safety of cilazapril in elderly patients with essential hypertension. A multicenter study [32].
• Radionuclide scintigraphy was performed with cilazapril and placebo, given one week apart [18].
• The overall incidence of adverse events observed during cilazapril therapy is comparable with that seen with placebo in double-blind studies [33].

References