Disease relevance of PERINDOPRIL

• Adverse event with first-dose perindopril in congestive heart failure [1].
• Blood pressure, forearm arterial hemodynamics (with a pulsed Doppler flowmeter), and echocardiographic parameters were studied in 16 patients with sustained essential hypertension before and 3 months after administration of the converting enzyme inhibitor perindopril [2].
• Treatment of DS rats with the CEI perindopril (4.56 mg x kg(-1) x d(-1)) did not affect SBP (225+/-6 mm Hg) but modestly improved EDR (ED50: 6.07+/-.37; P<.05 versus hypertensive DS) as well as proteinuria and glomerular histology [3].
• METHODS AND RESULTS: Sixteen patients with ischemic heart disease were treated either with perindopril (4 mg/d PO) for up to 36 days before surgery (n = 9) or without the inhibitor as control subjects (n = 7) [4].
• The aim of the present study was to examine the in vivo effect of candesartan (CA), a clinically used AT(1)-R blocker (ARB), and perindopril (PE), an angiotensin-converting enzyme (ACE) inhibitor (ACE-I), on pig serum-induced liver fibrosis development in rats [5].

Psychiatry related information on PERINDOPRIL

• Effects of blood pressure lowering with perindopril and indapamide therapy on dementia and cognitive decline in patients with cerebrovascular disease [6].
• RESULTS: The primary end point occurred in 181 patients (35%) taking perindopril and 290 patients (57%) taking placebo, with a significant absolute risk reduction of 0.22 (95% confidence interval, 0.16 to 0.28; P<.001) [7].
• At 12 weeks, glomerular filtration rate was higher in the perindopril treated group when compared to the triple therapy group, but neither group treated with antihypertensive therapy was different to untreated diabetic rats [8].

High impact information on PERINDOPRIL

• Perindopril completely abolished the biosynthesis of PDGF-AB but had little effect on residual FGF-2 [9].
• CONCLUSIONS: The ability of ACE inhibitors such as perindopril to attenuate neointima formation and growth in balloon catheter-injured rat carotid arteries is dependent on early events in the media, the inhibition of SMC PDGF-AB biosynthesis and attenuation of proliferation [9].
• In the internal mammary artery, free ACE was similarly inhibited by perindopril in the endothelium (P < .05) and adventitia (P < .05), and the free ACE-to-total ACE ratio, an index of ACE inhibition, was markedly decreased by perindopril in parallel in the endothelium (P < .001) and adventitia (P < .001) [4].
• These results indicate that perindopril effectively penetrates the vascular wall to inhibit ACE in the adventitia, thus providing evidence that perindopril may be beneficial in inhibiting both circulating Ang II and its local formation in the vascular wall [4].
• The present study was undertaken to assess the sites and extent of in vivo inhibition of ACE by long-term perindopril treatment in different layers of the internal mammary artery in patients with ischemic heart disease [4].

Chemical compound and disease context of PERINDOPRIL

• Angiotensin-converting enzyme inhibition in mild hypertension with concomitant diseases and therapies: an efficacy, safety, and compatibility study of novel design, the Perindopril Therapeutic Safety Study [10].
• METHODS: Forty-five patients with hypertension were randomly assigned to three groups: 16 patients were treated with perindopril (4 mg/day) for four weeks; 15 were treated with losartan (50 mg/day) for four weeks; and 14 were not treated with either perindopril or losartan (control group) [11].
• Antihypertensive efficacy and safety of perindopril in mild-to-moderate essential hypertension: results of a double-blind multicenter study versus atenolol [12].
• Both aminoguanidine and perindopril retarded the increase in albuminuria, which was completely abrogated by combination therapy [13].
• RESULTS: Despite a similar reduction in blood pressure by perindopril and oma10, greater attenuation of albuminuria was afforded by oma10, with a complete amelioration observed with oma40 [14].

Biological context of PERINDOPRIL

• Neointimal cell proliferation 10 days after injury was unaffected by perindopril, although neointima size was reduced by 30% [9].
• CONCLUSIONS: Perindopril and losartan similarly augment BK-induced coronary vasodilation [11].
• Perindopril treatment shifted the baroreflex curves back towards the WKY curves [15].
• CONCLUSION: We found that 1-year treatment with 8 mg/d of perindopril reduces progressive left ventricular remodeling that can occur even in the presence of small infarct size, but it was not associated with better clinical outcomes [7].
• METHODS: In phase I, 57 children with DMD and a left ventricular ejection fraction (LVEF) >55% (mean 65.0 +/- 5.4%), 9.5 to 13 years of age (mean 10.7 +/- 1.2 years), were enrolled in a three-year multicenter, randomized, double-blind trial of perindopril, 2 to 4 mg/day (group 1), versus placebo (group 2) [16].

Anatomical context of PERINDOPRIL

• CONCLUSIONS: The present demonstrates that long-term administration of perindopril potently inhibits both endothelial and adventitial ACE to a comparable degree in the human internal mammary artery [4].
• Pretreatment with perindopril increased bone marrow cellularity and the number of hematopoietic progenitors (granulocyte macrophage colony-forming unit [CFU-GM], erythroid burst-forming unit [BFU-E], and megakaryocyte colony-forming unit [CFU-MK]) from day 7 to 28 after irradiation [17].
• Perindopril also increased the number of hematopoietic stem cells with at least a short-term reconstitutive activity in animals that recovered from irradiation [17].
• The mean increase in left ventricle end-diastolic volume was 0.7 mL with perindopril compared with 4.0 mL with placebo (P<.001) [7].
• The European trial on reduction of cardiac events with perindopril in stable coronary artery disease (EUROPA) [18].

Associations of PERINDOPRIL with other chemical compounds

• METHOD: Streptozotocin-induced diabetic spontaneously hypertensive rats were randomised to no treatment, the ACE inhibitor, perindopril (2 mg/l), the AGE formation inhibitor, aminoguanidine (1 g/l) and a combination of both agents and were followed for 32 weeks [13].
• In conclusion, treatment with perindopril in NIDDM patients had no adverse effects on plasma lipids, glucose tolerance, or insulin sensitivity [19].
• After 1 month of placebo (T0), perindopril was given for 12 months (T12) to 17 hypertensive type II diabetics, treated either by insulin, sulfonylurea, and/or biguanide [20].
• AIMS: The aim of this study was to assess the effect of the angiotensin converting enzyme inhibitor perindopril on cardiovascular events in diabetic patients with coronary artery disease [21].
• The reduction in blood pressure with atenolol (drop in mean blood pressure 28.4 +/- 1.8 mm Hg) was greater than with perindopril (20.6 +/- 1.8 mm Hg, P < .05) [22].

Gene context of PERINDOPRIL

• All diabetes-associated changes in MMP and TIMP mRNA and activities were attenuated by perindopril treatment in association with reduced type IV collagen accumulation [23].
• There was a correlation between both the amount of VEGF in myocardium and the number of capillaries (r = 0.88; P <.01) and VEGF and eNOS expression in myocardial capillaries (r = 0.93; P <.01) in OZR treated with perindopril [24].
• By contrast, AT(1) receptor binding in vascular smooth muscle cells was increased by 80% in patients treated with perindopril as confirmed by immunocytochemistry. eNOS was expressed primarily in endothelial cells, whereas little iNOS expression occurred in vascular smooth muscle cells of untreated patients [25].
• Both eNOS and iNOS expression seemed to increase during perindopril treatment [25].
• These results indicated that the beneficial effects of Astragalus and Perindopril for treating viral myocarditis might be partly mediated by preserving the functions of SERCA 2 activity and ET system [26].

Analytical, diagnostic and therapeutic context of PERINDOPRIL

• In a single-blind study versus placebo, it was shown that perindopril significantly reduced blood pressure (p less than 0.01), whereas there was an increase in brachial blood flow (p less than 0.01) because of a simultaneous increase in blood flow velocity (p less than 0.01) and arterial diameter (p less than 0.01) [2].
• Thirty Sprague-Dawley rats were randomly assigned to sham surgery, subtotal nephrectomy (STNx) alone or STNx treated with the ACE inhibitor, perindopril, and sacrificed after 12 weeks [27].
• Ten patients with NIDDM and moderate hypertension were studied in a double-blind, placebo-controlled, crossover study encompassing 6 weeks of placebo treatment and 6 weeks of perindopril treatment given in random order [19].
• In the perindopril group, 40 deaths (6%) and 22 hospitalizations (4%) for heart failure occurred, whereas 37 deaths (6%) and 30 hospitalizations (5%) occurred in the placebo group [7].
• Repair of coronary arterioles after treatment with perindopril in hypertensive heart disease [28].

References