A comparative evaluation of neuroprotective activity of perindopril and valsartan in rats

Background: Angiotensin II receptor blockers and Angiotensin-converting enzyme inhibitors are widely used drugs for cardiovascular disorders, renal disease, and diabetes. Recently, they have been recognized for neuroprotective activity and are used in many brain disorders. Aim and Objective: The present study was done to explore effects of perindopril and valsartan on experimentally induced learning and memory impairment in Wistar rats. Materials and Methods: 40 Wistar rats were divided into 5 groups, eight rats in each group, namely normal control, disease control, positive control (Piracetam 600 mg/kg), test group I (Perindopril 4 mg/kg), and test group II (Valsartan 15 mg/kg). Except normal control group, all animals received intraperitoneal injection of Scopolamine 1 mg/kg for 21 days to induce memory impairment. Piracetam and Test drugs were administered once daily orally for 21 consecutive days. On day 0, 7th, 14th, and 21st of the experiment, muscle grip strength (Wire hanging grip test) and memory functions Elevated plus maze (EPM) of all the animals were assessed. On 8th, 15th, and 22nd day of the experiment, retention memory functions (EPM) were assessed. Results: Animals treated with Scopolamine showed significant reduction in grip strength and significant rise in transfer latency (TL) (EPM model). Rats treated with piracetam and test drugs showed significant increase in grip strength. The animals treated with piracetam and test drugs showed significant reduction in TL (EPM model) when compared with disease control group. Similar results were seen in retention memory test. Conclusion: Perindopril and valsartan demonstrated neuroprotective effect in scopolamine-induced memory impairment in rats. Memory improvement by these test drugs was comparable with positive control piracetam.

Determination of perindopril erbumine by oxidative coupling reaction using 2, 6-dichloroquinone-4-chlorimide

Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 µg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines

Effects of perindopril on bone turnover markers and bone mineral density in osteoporotic rats / 中华老年医学杂志

Objective To explore the effects of peridopril on osteoporosis and possible mechanisms involved.Methods Fifty experimental rats were divided into a normal control group,a sham operation group(Sham group),an ovariectomized group(OVX group),a perindopril group and an estrogen group (E2 group),with ten in each group.The perindopril group was intragastrically administered perindopril 4 mg/kg per day,the E2 group was intragastrically administered estrogen 1.2 mg/kg per day,and rats in the normal control group,the sham group and the OVX group were intragastrically given an equal volume of distilled water.Drugs were given once a day for 12 weeks.After 12 weeks of drug intervention,all rats were anaesthetized and 12 ml blood was extracted from the heart,and serum calcium,phosphorus,alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase(TRACP) were determined by enzyme-linked immunosorbent assays.The bone mineral density(BMD)of the left femur was measured by dual energy X-ray absorptiometry.Results After 4 weeks of drug intervention,the femur BMD was lower in the OVX group than in the sham operation group and the normal control group(F =12.224,P＜0.05),and there was no difference between the sham operation group and the normal control group(P＞0.05).After 12 weeks of drug intervention,serum Ca and P levels had no significant difference between the groups(P＞0.05).ALP and TRACP levels in the OVX group were (192.30± 14.50) U/L and (12.7 ± 1.72) U/L,respectively,which were significantly higher than those in the sham operation group(P＜0.01).ALP and TRACP levels in the perindopril group were (169.00 ± 10.14) U/L and (10.19 ± 1.24) U/L,respectively,which were lower than those in the OVX group(P＜0.05).ALP and TRACP levels in the E2 group were (130.76±9.47) U/L and (7.04±0.96) U/L,respectively,which were lower than those in the OVX group(P＜0.01).BMD in the OVX group was (0.161±0.011) g/cm2,which was lower than that in the sham operation group (P ＜ 0.01).BMD in the perindopril group was (0.173 ± 0.011) g/cm2,which was higher than that in the OVX group(P ＜0.05).After estrogen treatment,BMD of the E2 group was (0.196±0.008) g/cm2,which was higher than that in the OVX group(P ＜0.01).Conclusions Perindopril can decrease high bone turnover,increase bone density in ovariectomized rats,and thus may be used for alleviating postmenopausal osteoporosis.

Improvement Effects of 3 Kinds of Angiotensin Converting Enzyme Inhibitor on Ventricular Remodeling in Patients with Acute Myocardial Infarction / 中国药房

OBJECTIVE: To observe the improvement effects of angiotensin converting enzyme inhibitor (ACEI) fosinopril, perindopril and benazepril on ventricular remodeling in patients with acute myocardial infarction (AMI), and to evaluate its safety. METHODS: A total of 96 AMI patients selected from our hospital during Jan. 2014-Oct. 2016 were divided into group A, B, C according to random number table, with 32 cases in each group. All patients received symptomatic treatment, underwent percutaneous coronary intervention, and then given ACEI after blood vessels recanalization and keeping blood pressure stable. Group A was given Fosinopril sodium tablets 10 mg, qd; group B was given Perindopril tert-butylamine tablets 4 mg, qd; group C was given Benazepril hydrochloride tablets 10 mg, qd. All groups were treated for consecutive 6 months. Cardiac structure and function indexes (LVESD, LVEDD, IVSD, LVPWD, LVEF, CO), hemodynamic indexes (SBP, DBP, HR) and related lab indexes (FPG, TG, TC, HDL-C, LDL-C, AST, ALT, Scr, BUN) of 3 groups were observed before and after treatment. The occurrence of ADR was recorded. RESULTS: Before treatment, there was no statistical significance in cardiac structure and function indexes, hemodynamic indexes or related lab indexes among 3 groups (P＞0. 05). After treatment, the levels of LVESD, LVEDD, LVPWD, CO, HR, FPG, TG, TC and LDL-C in 3 groups were decreased significantly, while the levels of LVEF and SBP were increased significantly, with statistical significance (尸＜0. 05). There was no statistical significance in above indexes among 3 groups after treatment (P＞0. 05). After treatment, the level of Scr in group B was significantly increased and higher than group A and C, with statistical significance (P＜0. 05). There was no statistical significance in the levels of IVSD, DBP, HDL-C, AST, ALT or BUN among 3 groups before and after treatment as well as the level of Scr between group A and C (P＞ 0. 05). There was no statistical significance in the incidence of ADR among 3 groups(P＞0. 05). CONCLUSIONS: Fosinopril, perindopril and benazepril can significantly improve ventricular remodeling in AMI patients, narrowing the heart cavity, increasing systolic pressure, lowering heart rate, reducing the oxygen consumption of the ventricle, with similar effects. Perindopril may increase the level of Scr, so fosinopril and benazepril are safe and suitable for AMI patients with renal function disorder.

The association between Gal-3 and the effect of perindopril on ventricular remodelin / 重庆医学

Objective To investigate the association between Gal-3 and the effect of perindopril on ventricular remodeling in ischemic heart failure rabbit.Methods A rabbit model of ischemic heart failure was made by ligationof the anterior descending branch of the coronary artery.Thirty rabbits were divided into sham operation group,heart failure group and perindopril group.Determination of cardiac function by echocardiography after 4 weeks of treatment respectively;mRNA expression and protein content of Gal-3 were detected by Real-time PCR or Western-blob.Serum Gal-3 level was determinated by ELISA.Results Compared with sham operation group,mRNA expression and protein content of Gal-3,type Ⅰ collagen and type Ⅲ collagen increased and the serum level of Gal-3 increased in heart failure group(P＜0.05);compared with heart failure group,mRNA expression and protein content of Gal-3,type Ⅰ collagen and type Ⅲ collagen decreased and the serum level of Gal-3 was reduced in perindopril group(P＜ 0.05).Gal-3 was negativelycorrelated with heart function(r=-0.925,P＜0.05).Conclusion Effect of perindopril inhibiting myocardial fibrosis,slowing the ventricular remodeling and improving heart function associated with level of Gal-3.

Simultaneous determination of indapamide, perindopril and perindoprilat in human plasma or whole blood by UPLC-MS/MS and its pharmacokinetic application / 药物分析学报

Simple and sensitive methods were developed for the determination of indapamide, perindopril and its active metabolite perindoprilat in human plasma or whole blood by hyphenated ultra-performance li-quid chromatography-mass spectrometry (UPLC-MS/MS). Indapamide-d3, perindopril-d4 and perindo-prilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18column (4.6 mm × 100 mm, 2.4 μm) for indapamide and perindopril simultaneously following a protein precipitation pretreatment of the biosamples. The separation of perindoprilat was achieved in-dependently on a phenomenex PFP column (4.6 mm × 150 mm, 5 μm). All the analytes were quantitated with positive electrospray ionization and multiple reactions monitoring mode. The assay exhibited a linear range of 1–250 ng/mL for indapamide, 0.4–100 ng/mL for perindopril and 0.2–20 ng/mL for peri-ndoprilat. The methods were fully validated to meet the requirements for bioassay in accuracy, precision, recovery, reproducibility, stabilities and matrix effects, and successfully applied to the pharmacokinetic study of perindopril tert-butylamine/indapamide compound tablets in Chinese healthy volunteers and the comparative pharmacokinetic study between plasma and whole blood.

Therapeutic effect and safety of perindopril combined amlodipine and valsartan combined amlodipine on hypertension / 心血管康复医学杂志

Objective :To observe therapeutic effect and safety of perindopril combined amlodipine (P+ A) and valsartan combined amlodipine (V+A) on hypertension .Methods :A total of 126 patients with hypertension treated in our hospital were enrolled.The patients were randomly and equally divided into V + A group and P+ A group ,both groups received corresponding treatment based on routine intervention for 12 weeks.Levels of systolic blood pressure (SBP) ,diastolic blood pressure (DBP) ,heart rate (HR) ,plasma nitric oxide (NO) ,endothelin (ET)-1 ,von Willebrand factor (vWF) ,serum cystatin C (CysC) and uric acid (SUA) before and after treatment ,therapeutic effect and incidence rate of adverse reac-tions were observed and compared between two groups .Results :Total effective rate of V+A group was significantly higher than that of P+A group (92.06% vs.79.37%) , P＝0.042. Compared with before treatment ,after 12-week treatment , there were significant reductions in levels of SBP ,DBP ,plasma ET-1 and vWF ,and significant rise in plasma NO level in two groups ;significant rise in serum CysC level in V+A group , P＝0.001 all.Compared with P+A group after 12-week treatment ,there were significant reductions in levels of DBP [(85.34 ± 6.27)mmHg vs.(80.25 ± 6.31)mmHg] ,SBP [(130.33 ± 10.18)mmHg vs.(125.61 ± 10.25)mmHg] ,plasma ET-1 [(63.48 ± 9.30)pg/ml vs.(54.32 ± 9.21) pg/ml] , vWF [(125.78 ± 13.37)% vs.(113.54 ± 13.26)% ] and serum CysC [(1.41 ± 0.31)mg/L vs.(0.89 ± 0.25)mg/L] ,and significant rise in plasma NO level [(75.48 ± 10.65) μmol/L vs.(82.94 ± 10.56)μmol/L] in V+A group ,P＜0.05 or ＜0.01. There was no significant difference in incidence rate of adverse reactions between two groups , P＝0.143. Conclu-sion :Valsartan and perindopril respectively combined amlodipine can effectively reduce blood pressure level in hypertensive patients ,but the former can more significantly improve vascular endothelial function with better therapeutic effect .

Effects of perindopril at different doses on cardiac function and ACE2/Ang-(1-9)/Ang-(1-7) axis of ischemic cardiac dysfunction rabbits / 中国病理生理杂志

[ ABSTRACT] AIM:To investigate the different dose of perindopril on cardiac function in the rabbits with ische-mic cardiac dysfunction .METHODS:Male rabbits weighing 2.5~3.0 kg ( n=30) were randomly divided into 3 groups (n=10):high dose perindopril group (HD group), low dose perindopril group (LD group) and cardiac dysfunction group (CD group).The Left anterior descending coronary artery of the rabbits was ligatured for model preparation .In HD group, the rabbits were treated with perindopril split normal saline solution (1 g/L)2 mL· kg-1 · d-1 .In LD group, the rabbits were treated with perindopril split normal saline solution (0.33 g/L)2 mL· kg -1 · d-1.In CD group, the rabbits were treated with normal saline solution 2 mL· kg-1 · d-1 .Four weeks after treatment , the cardiac function was measured via echocardiography , the mRNA expression of angiotensin-converting enzyme 2 ( ACE2 ) and angiotensin type 2 receptor (AT2R) was analyzed by real-time PCR, serum angiotensin (Ang)-(1-9) and Ang-(1-7) levels were detected by ELISA. RESULTS:Compared with CD group , the cardiac function of the 2 groups treated with perindopril was significantly im-proved (P<0.01), and more improvement in HD group was observed than LD group (P<0.05).The serum angiotensin ( Ang)-(1-9) and Ang-(1-7) level and the mRNA expression of ACE 2 and AT2R in the 2 groups treated with perindopril were significantly improved (P<0.01).Compared with LD group, the mRNA expression of ACE2 and AT2R and the ser-um levels of Ang-(1-9) in HD group were significant improved (P<0.05), while no difference of serum Ang-(1-7) level was observed.Correlation analysis revealed that the improvement of the cardiac function was associated with serum Ang -(1-9) level, mRNA expression of ACE2 and AT2R (P<0.01), but has no significant correlation with serum Ang-(1-7) lev-el.CONCLUSION:High dose of perindopril may improve more cardiac function in ischemic cardiac dysfunction model in rabbits.The mechanism may relate to increasing serum Ang-(1-7) level to activate AT2R.

Effect of bisoprolol combination with perindopril and spironolactone on chronic heart failure caused by rheumatic heart disease / 中国基层医药

Objective To evaluate the combination treatment effects of bisoprolol,perindopril and spirono-lactone on chronic cardiac failure caused by rheumatic heart disease.Methods 92 patients were randomly divided into the control group (n=45) and observation group (n=47).The observation group received combination usage of bisoprolol,perindopril and spironolactone,while the control group was given regular treatment.Cardiac functions were measured in both two groups.Results The left ventricular end diastolic diameter ( LVEDD) and left ventricular end systolic diameter (LVESD) were significantly decreased in the observation group(t=4.217,5.842,P<0.05),while left ventricular ejection fraction (LVEF) was significantly increased compared with the control group (t=3.164,P<0.05).Conclusion The combination treatment effects of bisoprolol,perindopril and spironolactone has the privilege effects on chronic cardiac failure caused by rheumatic heart disease,which mainly improves cardiac remodeling.

Neuroprotective effect of renin angiotensin system blockers on experimentally induced Alzheimer’s disease in rats.

Background: Alzheimer’s disease (AD) is a major world-wide health problem. Much evidence points to a link between hypertension and AD. However, the exact effects of different antihypertensive drugs on AD need to be more assessed. The aim was to evaluate and compare the possible effects of perindopril, and candesartan on cognitive impairment, oxidative stress markers, and brain concentrations of amyloid beta-peptide (Aβ-P) in a rat model of induced dementia. Methods: Thirty-two adult male Wistar rats were distributed among 4 groups; (1) normal controls; (2) rats with dementia induced by intracerebroventricular administration of streptozotocin (ICV-STZ) and received no treatment; (3) ICV-STZ rats treated orally with perindopril for 3 weeks; and (4) ICV-STZ rats treated orally with candesartan for 3 weeks. The assessed parameters were spatial memory by Morris Water Maze test, brain tissue level of total antioxidant capacity (TAC), reduced glutathione (GSH), lipid peroxidation product (malondialdehyde [MDA]), and Aβ-P. Results: Both perindopril and candesartan attenuated STZ-induced memory impairment, caused a significant increase in TAC and GSH levels, reduced MDA levels, whereas only candesartan significantly reduced Aβ-P levels. Conclusions: This study reports that candesartan and perindopril can reverse the free radical induced damages and resultant memory defects, and may suggest candesartan as worthy drugs for prevention of Aβ-P deposition in this animal model of AD.

Comparison of the effect of perindopril and metoprolol in the treatment of diabetic patients with asymptomat-ic cardiac insufficiency / 中国基层医药

Objective To compare the curative effect of perindopril and metoprolol in the treatment of diabetic patients with asymptomatic cardiac insufficiency.Methods According to the method of random numbers, 152 diabetic patients with asymptomatic cardiac insufficiency were divided into the observation group and control group,with 76 cases in each group.The observation group was given with perindopril treatment,while control group was given with metoprolol treatment.The cardiac function index,glycosylated hemoglobin,BNP levels,the incidence of cardiac insufficiency and the occurrence of adverse drug reactions before and after treatment were compared.Results There were no significant differences in LVEF,Tei index and E/A between two groups before treatment (all P >0.05 ).Compared with before treatment,the cardiac function indexes of the two groups were significantly improved after treatment(t=5.96,4.83,4.91,10.22,5.68,5.18,all P0.05),and the difference between the two groups was not statistically significant(all P>0.05).The BNP levels of the observation group before and after the treatment were (515.43 ± 58.85)pg/mL and (214.43 ±32.42)pg/mL respectively,of which the control group were (513.94 ±59.11)pg/mL and (263.32 ±43.31)pg/mL respectively,and after treatment,the BNP levels of the two groups were significantly decreased(t=23.45,17.68,all P0.05).Conclusion Using perindopril in treatment of diabetic patients with asymptomatic heart function can obviously improve cardiac function,reduce the incidence of BNP and cardiac insuffi-ciency.It has the clinical curative effect and high safety.

Effect of Different Doses of Perindopril on Endothelial Progenitor Cells and Vascular Endothelial Function in Patients With Coronary Artery Disease / 中国循环杂志

Objective: To investigate the effect of different doses of perindopril on peripheral endothelial progenitor cells (EPCs) and vascular endothelial function in patients with coronary artery disease (CAD) . Methods: A total of 84 CAD patients with coronary angiography confirmed diagnosis were divided into 3 groups: Control group, the patients received routine medication, n=27. Low-dose group, the patients received routine medication with perindopril for 4mg, n=29. High-dose group, the patients received routine medication with perindopril for 8mg, n=28. All patients were treated for 12 weeks. The EPCs level was detected by flow cytometry assay, flow-mediated-dilation (FMD) function in brachial artery was measured by ultrasound and plasma levels of high sensitivity C-reactive protein (hs-CRP), angiotensin II (AngII) were examined in all groups. Results: ① After12 weeks of treatment, the EPCs level and FMD function had certain improvement, hs-CRP level decreased in various degrees in all 3 groups, P group showed increased EPCs level and FMD function, decreased levels of hs-CRP and AgnII, P Conclusion: Perindopril may mobilize peripheral EPCs at certain point, and therefore improve endothelial function, the higher dose of perindopril may have better effect.

Perindopril down-regulates scavenger receptor A expression in renal tubulointerstitium of diabetic rats / 重庆医学

Objective To investigate the effect of an ACE inhibitor ,perindopril ,on the expression of SR‐A in renal tubuloint‐erstitium of diabetic rats .Methods Diabetes was induced in male Sprague‐Dawley rats by injection with streptozotocin .The rats were then randomly divided into 3 groups:normal control group;untreated diabetes mellitus group and diabetes mellitus group trea‐ted with perindopril .After a 24‐week treatment ,tubulointerstitial injury index was assessed with Masson′s trichrome sections .The expression of SR‐A mRNA was detected by RT‐PCR and the expression of SR‐A protein in renal tubulointerstitium was detected by immunohistochemistry .Results The tubulointerstitial injury index ,the expression of SR‐A mRNA were significantly higher in the diabetes group than those in normal control group .Perindopril treatment not only attenuated the tubulointerstitial injury ,but also reduced the overexpression of SR‐A mRNA in diabetic rats .The expression of SR‐A protein was most obvious in renal tubulointer‐stitium in diabetic rats ,which was obviously attenuated by perindopril treatment(P<0 .05) .Conclusion The findings of the this study indicate that perindopril may have renoprotective effects on diabetic nephropathy via inhibiting the expression of SR‐A in re‐nal tubulointerstitium .

Importância da proteção cardiovascular durante o tratamento da hipertensão arterial: diferenças entre os agentes inibidores do sistema renina-angiotensina-aldosterona / Importance of cardiovascular protection during arterial hypertension treatment: differences among renin-angiotensin-aldosterone system inhibitors

A inibição do sistema renina-angiotensina-aldosterona (SRAA) demonstrou ser fundamental não somente no controle da hipertensão arterial, mas também na redução da progressão de doenças cardíacas, renais e vasculares, com impacto positivo na morbimortalidade. Diversas evidências revelam que o SRAA participa ativamente da origem da hipertensão arterial, com relação no desenvolvimento de obesidade, dislipidemia, resistência à insulina e doença crônica renal, além de ser o responsável pela homeostase eletrolítica. A ativação do SRAA se associa com níveis elevados de enzima conversora de angiotensina (ECA) e expressão aumentada de angiotensinogênio, fatores esses que levam ao aumento de angiotensina II, responsável por estresse oxidativo, vasoconstrição, hiperatividade do sistema nervoso simpático e aumento da reabsorção de sódio. O SRAA pode ser inibido em diferentes estágios e por mecanismos diversos, sendo que a forma como é inibido tem influência no prognóstico. E, dentre essas opções, há evidências claras do melhor benefício sobre a redução da mortalidade por todas as causas e da mortalidade cardiovascular com o uso dos inibidores da ECA (IECA) sobre os bloqueadores de receptores AT1 (BRA). Dentre os diferentes IECA, o perindopril, através de suas características específicas e benefícios clínicos comprovados em estudos randomizados de maior impacto, garante uma superioridade na proteção cardiovascular durante o tratamento dos pacientes hipertensos. Cabe destacar que os estudos que deram origem aos IECA tiveram a participação de pesquisadores brasileiros, com destaque para o Professor Sérgio Ferreira (Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto)

Renin-angiotensin-aldosterone system (RAAS) inhibition has demonstrated to be crucial not only to control arterial hypertension but also to reduce the progression of cardiac, renal and vascular diseases, with positive impact on morbidity-mortality. There is evidence revealing that RAAS participates actively on arterial hypertension origin, also taking part on obesity, dyslipidemia, insulin resistance and chronic renal disease, besides being responsible for electrolytic homeostasis. RAAS activation is associated with elevated levels of angiotensin conversion enzyme (ACE) and angiotensinogen overexpression, factors which increase angiotensin II, that induces oxidative stress, vasoconstriction, sympathy nervous systemhyperactivity and sodium reabsorption increase. RAAS may be inhibited in different stages and through different mechanisms, and the way it is inhibited is linked to prognosis. Among available options, there is clear evidence of a better benefit over all cause and cardiovascular mortality reduction when using ACE inhibitors (ACEI) over AT1 receptor blockers (ARB). Among different ACEI, perindopril, through its specific characteristics and clinical benefits proved on high level randomized trials guarantees a superior cardiovascular protection while treating hypertensive subjects. It's nice to highlight that Brazilian researches, mainly Professor Sérgio Ferreira (Hospital das Clínicas da Universidade de São Paulo, Ribeirão Preto), took part on the studies that discovered ACEIs.

Study of changes in serum lipid profile and blood sugar level by perindopril and telmisartan during treatment of systemic hypertension.

Background: This study was designed to compare adverse effects on serum lipid profile and blood sugar level in the treatment with two commonly used drugs perindopril and telmisartan in cases of hypertension. This was an “observational” and “cross-sectional” study. Methods: A total of 100 patients were included in each, Groups A and B. In both groups, half the patients were given perindopril 4 mg OD and half were given telmisartan 40 mg OD for 24 weeks. Total cholesterol (TC), high density lipoprotein (HDL), low density lipoprotein (LDL), triglycerides (TG), fasting blood sugar (FBS), and postprandial blood sugar (PPBS) level was estimated initially and then at 4th, 12th, and 24th week. Statistical analysis was done using ANOVA. Results: With perindopril initial means of TC, HDL, LDL, TGs, FBS, and PPBS in Groups A and B were 190.32, 49.76, 117.96, 165.04, 84.56, 122.60, and 188.80, 51.64, 118.52, 159.12, 93.92, 133.60, respectively. After 24 weeks, these values were 190.84, 50.68, 118.60, 163.84, 83.48, 120.20, and 190.96, 52.04, 118.28, 157.56, 93.96, 133.68, respectively (p > 0.05). With telmisartan, initial means of TC, HDL, LDL, TG, FBS, and PPBS in both groups were 188.08, 49.76, 118.84, 167.20, 83.72, 120.68, and 188.08, 46.88, 121.96, 167.84, 91.44, 131.72, respectively. After 24 weeks, these values in both groups were 189.36, 49.80, 120.04, 165.96, 82.60, 118.36 and 186.12, 45.28, 121.08, 167.72, 92.76, 129.56 respectively (p > 0.05). Conclusions: It concluded that both perindopril and telmisartan had not any significant adverse effects on plasma lipid profile and blood sugar level in both groups.

Comparative Evaluation of Angiotensin-Converting Enzyme Inhibitors for their Beneficial Effects in Patients with Ischemic LV Systolic Dysfunction and Undergoing Coronary-Artery Bypass Surgery.

We compared three angiotensin-converting enzyme (ACE) inhibitors, captopril, perindopril, and ramipril, in the presented prospective study for their effectiveness in patients having left ventricular (LV) systolic dysfunction and undergoing coronaryartery bypass grafting (CABG). We enrolled 27 patients in captopril, 43 patients in perindopril, and 70 patients in ramipril group. There was about 25%–36% rise in LVEF after 3 and 6 months of ACE inhibitor administration in all three groups. The reduction in LV diameters did not differ significantly amongst the three groups. There was a significant decrease (p < 0.05) in LV end-diastolic diameter from baseline levels in captopril and perindopril groups after 3 months that got increased after 6 months but remained below pretreatment levels in both the groups. In ramipril group, there was no much change in this parameter from baseline levels at 3 and 6 months of treatment. After 6 months of treatment, the percent reduction in LV end-systolic diameter was also sustained in perindopril-treated patients. The percent reduction was greater in the perindopril group (3 and 6 months: 7.39 ± 5.94 and 7.73 ± 3.43, respectively) as compared to that observed in captopril group (3 and 6 months: 5.67 ± 1.05 and 2.52 ± 3.11, respectively) and ramipril group (3 and 6 months: 7.30 ± 2.75 and 4.93 ± 3.22, respectively). Mitral-valve regurgitation was greatly reduced in the captopril group at 3 as well 6 months of ACE inhibitor administration. However, the percent reduction from baseline levels was not statistically significant amongst the three groups. The percent improvement in functional status was significantly greater in the ramipril treatment group (36.46 ± 3.14) after 6 months of treatment as compared to that of captopril (6.67 ± 10.64) and perindopril (4.17 ± 2.73) group. In conclusion, our data show equal beneficial effects with all three ACE inhibitors under investigation in CABG patients with LV systolic dysfunction, with marginal superiority for perindopril.

Effect of blood pressure variability in patients with hypertension treated by amlodipine combined with perindopril / 中国医师进修杂志

Objective To observe the effect of blood pressure variability in patients with hypertension treated by amlodipine combined with perindopril.Methods From September 2012 to October 2013,patients with essential hypertension were given amlodipine 5 mg/d for 4 weeks,and 78 patients with blood pressure not reaching the standard after 4 weeks treatment were divided into group A and group B by random number table method,with 39 cases in each.Group A was given amlodipine 10 mg/d,and group B was given perindopril 4 mg/d on this basis (amlodipine 5 mg/d).Twenty-four hour ambulatory blood pressure was monitored in 2 groups by noninvasive portable ambulatory blood pressure monitoring in medication and 8 weeks after medication,measured values of standard deviation and coefficient of variation was used as a measurement of blood pressure variability.Results After 8 weeks of medication plus,24 h systolic blood pressure variability (24 h SSD),systolic blood pressure variability during the day (dSSD),nocturnal systolic blood pressure variability (nSSD),nocturnal systolic blood pressure variation coefficient (nSCV) and 24 h diastolic blood pressure variability(24 h DSD),diastolic blood pressure variability during the day (dDSD),nocturnal diastolic blood pressure variability (nDSD) in group A were significantly lower than those before medication plus[(13.22 ± 1.10) mmHg(1 mmHg =0.133 kPa) vs.(15.97 ± 1.65) mmHg,(12.04 ± 2.21) mmHg vs.(15.15 ±2.89) mmHg,(10.22 ±3.29) mmHg vs.(12.23 ±3.21) mmHg,0.093 ±0.021 vs.0.104 ± 0.017,(11.33 ± 2.09) mmHg vs.(13.27 ± 1.43) mmHg,(10.64 ± 1.81) mmHg vs.(12.57 ± 1.43) mmHg,(9.56 ± 1.32) mmHg vs.(11.23 ± 2.26) mmHg] (P ＜ 0.05),but there were no significant changes among 24 h systolic blood pressure variation coefficient (24 h SCV),systolic blood pressure variation coefficient during the day (dSCV) and 24 h diastolic blood pressure variation coefficient (24 h DCV),diastolic blood pressure variation coefficient during the day (dDCV),nocturnal diastolic blood pressure variation coefficient (nDCV) (P ＞ 0.05).After 8 weeks of medication plus,24 h SSD,24 h SCV,dSSD,dSCV and 24 h DSD,24 hDCV,dDSD,dDCV,nDSD in group B were significandy decreased compared with before combination plus[(10.23 ± 4.72) mmHg vs.(15.27 ± 3.23) mmHg,0.083 ± 0.032 vs.0.106 ± 0.019,(10.85 ± 3.29) mmHg vs.(15.09 ± 3.21) mmHg,0.080 ± 0.028 vs.0.096 ± 0.025,(10.13 ± 2.43) mmHg vs.(13.37 ±3.13) mmHg,0.111 ±0.035 vs.0.136 ±0.032,(9.58 ±2.49) mmHg vs.(12.29 ±3.27) mmHg,0.112 ± 0.036 vs.0.123 ± 0.04 1,(9.46 ± 2.78) mmHg vs.(11.19 ± 4.26) mmHg] (P ＜ 0.05),but there were no significant changes among nSSD,nSCV and nDCV (P ＞ 0.05).After 8 weeks of medication plus,24 h SSD,24 h SCV and 24 h DSD,24 h DCV,dSSD,dDSD,dSCV and dDCV in group B were significantly lower than those in group A (P ＜ 0.05).The nSSD,nDSD,nSCV and nDCV between 2 groups had no significant difference (P ＞ 0.05).Conclusions Amlodipine double dose or amlodipine single dose combined with perindopril can all effectively reduce the 24 hours' systolic and diastolic blood pressure variability,and the combined treatment is better and worthy of further promotion in clinic.

To evaluate the clinical curative effect of meglumine adenosine cyclophosphate combined with perindopril on patients with chronic congestive heart failure / 中华急诊医学杂志

Objective To explore the relationship of plasma NT-proBNP level and severity of chronic congestive heart failure (CHF) and investigate the curative effect and security of meglumine adenosine cyclophosphate (MAC) combined with perindopril on patients with CHF.Methods From June 2011 to June 2013,126 inpatients with chronic congestive heart failure were randomly divided into A group (42 cases,routine therapy),B group (41 cases,routine therapy and perindopril) and C group (43 cases,routine therapy and perindopril plus MAC),all cases treated for 14 days.The left ventricular ejection fraction (LVEF) and left ventricular end-diastolic diameter (LVEDD) by echocardiography and plasma NT-proBNP levels were evaluated before and after 14 days therapy.Results The plasma NT-proBNP levels in NYHA Ⅱ ～ Ⅳ classes were significantly difference compared each other between any two classes (P ＜0.05) and the levels was positively correlated with NYHA cardiac function class and LVEDD (r =0.617,P ＜ 0.01 ; r =0.412,P ＜ 0.01),negatively correlated with LVEF (r =-0.372,P ＜ 0.01).After 14 days therapy,compared with A group,the LVEF and LVEDD significantly improved (P ＜ 0.05) and NT-proBNP level significantly decreased (P ＜ 0.05) in B,C groups; Compared with B group,C group had lower NT-proBNP level (P ＜ 0.05) although no further improvement in cardiac function.Conclusions The plasma NT-proBNP level is correlated closely with the severity of CHF and it is a good examination of diagnose,therapy and evaluating prognosis of CHF.Perindopril may significantly decline plasma NT-proBNP level and improve cardiac function of CHF patients,combined with MAC may further decline plasma NT-proBNP level although not further improved LVEF.Giving MAC and perindopril to patients with CHF was secure and patients tolerated it well.

Study on the effect of perindopril and benazepril on nude mice bearing esophageal squamous cell carcinoma / 中华消化杂志

ObjectiveTo investigate whether there was inhibitory effect of angiotensin-Ⅰ converting enzyme inhibitors (ACEI) on esophageal carcinoma cell line.Methods The highest expression of vascular endothelial growth factor (VEGF) at mRNA level was screened in esophageal squamous cell carcinoma cell lines KYSE30,TE-1,EC109 and EC9706 by reverse transcriptionpolymerase chain reaction (RT-PCR) and which was transplanted and established nude mice xenografts model.After tumor formed,the nude mice were evenly divided into control group,perindopril group and benazepril group (n=6) of which 0.9％ saline,4 mg/kg perindopril and 6 mg/kg benazepril was given respectively to nude mice in each group.The tumor size and the tumor inhibitory rate were measured.The expression of CD31 in xenograft tumor was tested by immunohistochemistry and the microvessel density (MVD) was assessed.ResultsThe highest expression of VEGF at mRNA level was in EC9706 cell line.At second and third week,there was no significant difference in xenograft tumor size between each group. At fourth and fifth week,there was no significant difference in xenograft tumor size between perindopril group and control group,and the tumor inhibitory rate was 24.6 ％ and 21.1 ％.There was significant difference between benazepril group and control group (t=-2.450 and -3.120,P=0.035 and 0.008),and the tumor inhibitory rate was 33.1％ and 45.4％.After treated with perindopril and benazepril,the expression of CD31 in xenograft tumor of nude mice decreased.The MVD of benazepril group was significantly lower than that of control group (10.98±1.18 vs 13.98 ± 1.76； t =-3.732,P =0.002),and there was no significant difference between perindopril group (12.41±1.15) and control group (t=-2.053,P=0.07).ConclusionsBenazepril (6 mg/kg) could significantly inhibit the growth of EC9706 cell line formed xenograft tumor of nude mice.One of the possible tumor inhibitory mechanisms was inhibiting new vessel forming in tumor.Perindopril (4 mg/kg) may have the similar effect.

The effect of perindopril and metoprolol in the treatment of geriatric chronic heart failure / 中国基层医药

Objective To evaluate the clinical therapeutic efficacy of perindopril and metoprolol in the treatment of chronic heart failure in old patients( ≥60 years old).Methods 136 old patients( ≥60 years old) with chronic heart failure were randomly divided into the treatment group(n =68) and the control group(n =68).The control group received the routine treatment with digitalis,diuretics and nitroglycerin.The treatment group was given perindopril and metoprolol orally besides the routine treatment.The perindopril was taken orally 2mg per time,and once a day,and gradually raised to maximum does 8mg per time,once a day.The metoprolol was taken orally 25mg per time,twice a day,also gradually raised to maximum dose 25mg per time,twice a day.4-8 weeks were a treatment cycle.The cardiac function,left ventricular ejection fraction ( LVEF),the 6-minute walk and plasma brain natriuretic pep-tide (BNP) were observed before the beginning of the therapy and after,respectively.Results All patients improved their cardiac function,LVEF,plasma BNP and the 6-minute walk significantly after the therapy ( t =2.56,3.23,2.48,2.53,2.79,3.31,all P ＜ 0.05 ).The improvement of the treatment group was more significantly than that of the control group ( t =2.87,3.12,2.59,all P ＜ 0.05 ).The total effective rate of treatment group was 94.1％,significantly higher thar 70.6％ of control group( x2 =5.96,P ＜0.05 ).Conclusion The therapy of perindopril and metoprolol in old patients with chronic heart failure could improve ventvicular remodeling and the effect.