OBJECTIVETo investigate the role of perindopril for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP) in rabbits.

METHODSA total of 45 male New Zealand white rabbits (10 months old, weight 3.0 to 3.5 kg) were randomly divided into 3 groups involving normal control group (muscle injection of saline solution, n = 15, group NC), model group (muscle injection of dexamethasone, n = 15, group GIOP), and treatment group (muscle injection of dexamethasone combined with oral perindopril, n = 15, group GIOP+ACEI). All rabbits put to death after 12 weeks' treatment. The changes of bone mass and strength were observed and analyzed by bone histomorphology, biomechanics, metabolic bone related serological indexes and mRNA expression.

RESULTSAt 12 weeks, the analysis of bone histomorphology and biomechanics results showed that the bone mass and bone strength of group GIOP were significantly lower than that of group NC (P < 0.05); after perindopril treatment, the bone mass and bone strength of group GIOP+ACEI were higher obviously than that of group GIOP (P < 0.05). Mineralizing surface,mineral apposition rate and serum osteocalcin in group GIOP decreased than group NC; however, osteoclast number, osteoclast surface, eroded surface, and urinary deoxypyridinoline in group GIOP increased than group NC (P < 0.05); these changes were inhibited after perindopril treatment (P < 0.05). Quantitative RT-PCR revealed that after dexamethasone treatment, the ratio of SOST mRNS expression and RANKL/OPG mRNA expression obviously increased than that of group NC (P < 0.05); and Runx2 expression decreased significantly (P < 0.05); while the changes of mRNA expression were improved by perindopril treatment.

CONCLUSIONPerindopril can promote bone formation and inhibit bone resorption to deduce glucocorticoid-induced osteoporosis. This study provides a new method for prevention and treatment of GIOP.

Animals ; Biomechanical Phenomena ; Glucocorticoids ; adverse effects ; Male ; Osteoporosis ; chemically induced ; prevention & control ; Perindopril ; therapeutic use ; Rabbits

OBJECTIVEThe purpose of the present study was to evaluate the clinical efficacy of perindopril or losartan in combination with low-dose amiodarone on maintenance of sinus rhythm in patients with idiopathic paroxysmal atrial fibrillation (PAF).

METHODSOne hundred and eighty-one patients with idiopathic PAF were included in the study and randomly divided into three groups: group 1 (amiodarone group, n = 61) was treated with amiodarone alone, group 2 (amiodarone plus losartan, n = 59) was treated with amiodarone and perindopril in combination, and group 3 (amiodarone plus perindopril group, n = 61) was treated with amiodarone and perindopril in combination. The left atrial diameter (LAD) was measured with transthoracic echocardiogram at before and after 6, 12, 18 and 24-month of treatment. The duration of observation was up to two years and the primary end point of the study was the first recurrence of AF.

RESULTSDuring the 6 month following up, there was no difference in LAD among the three groups. After 12 months, LAD in group 1 was significantly larger than group 2 and group 3 (P < 0.05). At 7th-month, the sinus rhythm maintenance of group 1 was lower significantly than group 2 and group 3. At the end of the study, the maintenance of sinus rhythm in group 2 and group 3 was higher significantly than in group 1 (83.05% and 80.33% vs 59.01%, P < 0.05), nevertheless, there was no significant difference between group 2 and group 3.

CONCLUSIONSThe results of this study suggest that the combination of amiodarone with angiotensin converting enzyme inhibitor perindopril or with angiotensin II receptor antagonist losartan are more effective than amiodarone alone in sinus rhythm maintenance for idiopathic PAF. ACEI and ARB can inhibit the enlargement of left atrium and reduce recurrence rate in patients with idiopathic PAF.

Adult ; Aged ; Amiodarone ; therapeutic use ; Anti-Arrhythmia Agents ; therapeutic use ; Atrial Fibrillation ; drug therapy ; Drug Therapy, Combination ; Female ; Follow-Up Studies ; Humans ; Losartan ; therapeutic use ; Male ; Middle Aged ; Perindopril ; therapeutic use ; Prospective Studies

OBJECTIVETo investigate the influence of ACE inhibitor (perindopril) on the contractility and calcium transient and calcium handling proteins in ventricular myocytes from rats with experimental heart failure.

METHODSMale Wistar rats were randomized to heart failure group treated with perindopril (CHF-T, 3 mg.kg(-1).d(-1)), heart failure group without treatment (CHF-C) and sham-operated group (PS) after heart failure was induced by constricting abdominal aorta for 16 weeks. All groups were further followed up for 12 weeks. Left ventricular myocytes were isolated, and single cell shortening fraction and [Ca(2+)](i) were simultaneously measured through laser scanning confocal microscope under the field stimulation (1.0 Hz). RT-PCR and Western blot were performed to evaluate the level of mRNA and protein of Na(+)-Ca(2+) exchanger (NCX(1)), sarcoplasmic Ca(2+)-ATPase (SERCA(2)) and phospholamban (PLB).

RESULTSThe fraction of cell shortening (FS%) and [Ca(2+)](i max) (nmol/L) were significantly smaller in group CHF-C than group PS (FS%: 7.51 +/- 1.15 vs 13.21 +/- 1.49; [Ca(2+)](i max): 330.85 +/- 50.05 vs 498.16 +/- 14.07; both P < 0.01). And in CHF-T group, FS and [Ca(2+)](i max) were greater than those in CHF-C group. In CHF-C group, the left ventricular mRNA of NCX(1) and PLB were significantly higher than those in PS group (R(NCX)(1)/beta-Actin: 0.51 +/- 0.12 vs 0.19 +/- 0.06, P < 0.01; R(PLB)/beta-Actin: 0.26 +/- 0.12 vs 0.20 +/- 0.08, P = 0.045), yet SERCA(2) mRNA was lower than PS group (0.48 +/- 0.10 vs 0.80 +/- 0.11, P < 0.01). In CHF-T group, the mRNA levels of NCX(1) and SERCA(2) were just in the midst of the CHF-C and PS group, and had statistical significance respectively (all P < 0.05). In CHF - C and CHF - T group, the protein levels of NCX(1) were 1.141 +/- 0.047 and 1.074 +/- 0.081 times PS group, respectively (both P < 0.05), and SERCA(2) protein levels were respectively 0.803 +/- 0.100 and 0.893 +/- 0.084 times as high as in PS group (both P < 0.05). The protein expression of NCX(1) and SERCA(2) were also different between CHF-C and CHF-T groups (both P < 0.05).

CONCLUSIONACE inhibitor could improve cardiac function in CHF through directly enhancing the contractility of single myocardial cell, and these effects were probably mediated by its role in preventing the deleterious changes of calcium transient and calcium handling proteins in CHF.

Animals ; Calcium ; metabolism ; Calmodulin ; metabolism ; Heart Failure ; drug therapy ; metabolism ; Male ; Myocytes, Cardiac ; drug effects ; metabolism ; Perindopril ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar

Cardioprotective effect of fimasartan, a new angiotensin receptor blocker (ARB), was evaluated in a porcine model of acute myocardial infarction (MI). Fifty swine were randomized to group 1 (sham, n=10), group 2 (no angiotensin-converting enzyme inhibitor [ACEI] or ARB, n=10), group 3 (perindopril 2 mg daily, n=10), group 4 (valsartan 40 mg daily, n=10), or group 5 (fimasartan 30 mg daily, n=10). Acute MI was induced by occlusion of the left anterior descending artery for 50 min. Echocardiography, single photon emission computed tomography (SPECT), and F-18 fluorodeoxyglucose cardiac positron emission tomography (PET) were performed at baseline, 1 week, and 4 weeks. Iodine-123 meta-iodobenzylguanidine (MIBG) scan was done at 6 weeks for visualization of cardiac sympathetic activity. Left ventricular function and volumes at 4 weeks were similar between the 5 groups. No difference was observed in groups 2 to 5 in SPECT perfusion defect, matched and mismatched segments between SPECT and PET at 1 week and 4 weeks. MIBG scan showed similar uptake between the 5 groups. Pathologic analysis showed similar infarct size in groups 2 to 5. Infarct size reduction was not observed with use of fimasartan as well as other ACEI and ARB in a porcine model of acute MI.
3-Iodobenzylguanidine ; Angiotensin II Type 1 Receptor Blockers/therapeutic use ; Angiotensin Receptor Antagonists/*therapeutic use ; Angiotensin-Converting Enzyme Inhibitors/therapeutic use ; Animals ; Anterior Wall Myocardial Infarction/*drug therapy/physiopathology ; Biphenyl Compounds/*therapeutic use ; Cardiotonic Agents/*therapeutic use ; Disease Models, Animal ; Echocardiography ; Fluorodeoxyglucose F18 ; Perindopril/therapeutic use ; Positron-Emission Tomography ; Pyrimidines/*therapeutic use ; Random Allocation ; Swine ; Tetrazoles/*therapeutic use ; Tomography, Emission-Computed, Single-Photon ; Valsartan/therapeutic use ; Ventricular Function, Left/*physiology

OBJECTIVETo evaluate the effects of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin II type 1 receptor (AT-1 receptor) blocker on the progression of rat pulmonary fibrosis induced by bleomycin A5.

METHODSTwenty-four male Wistar rats were randomized into pulmonary fibrosis model, perindopril treatment, losartan treatment and control groups. In the former 3 groups, pulmonary fibrosis was induced via intratracheal injection of bleomycin A5 (5 mg/kg), after which the rats in the perindopril and losartan groups received intragastric administration of the corresponding agents at the daily dose of 2 mg/kg and 10 m/kg, respectively. The rats in the control group had intratracheal injection of normal saline only. In the 4th week, the histological changes of the lung tissues were examined microscopically with Masson staining. Hydroxyproline content in the lungs was measured, and the protein expressions of AT-1 receptor, TGF-beta1 and IkappaBalpha were examined using Western blotting. DNA binding activity of NF-kappaB was analyzed with electrophoretic gel mobility shift assay (EMSA), and zymography was used to assess the activity of matrix metalloproteinase-2 and 9 (MMP-2, 9).

RESULTSBoth perindopril and losartan treatment significantly reduced the pulmonary fibrosis score, content of hydroxyproline, protein expression of TGF-beta1, DNA binding activity of NF-kappaB and MMP-2, 9 activity, and increased cytoplasmic protein expression of IkappaBalpha. Perindopril treatment lowered the protein level of AT-1 receptor.

CONCLUSIONPerindopril and losartan may inhibit bleomycin A5-induced pulmonary fibrosis in rats by reducing the protein expression of TGF-beta1 and suppressing the DNA binding activity of NF-kappaB and MMP-2, 9 activity.

Angiotensin II Type 1 Receptor Blockers ; therapeutic use ; Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Bleomycin ; analogs & derivatives ; Blotting, Western ; Losartan ; therapeutic use ; Male ; NF-kappa B ; metabolism ; Perindopril ; therapeutic use ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; metabolism ; Random Allocation ; Rats ; Rats, Wistar ; Receptor, Angiotensin, Type 1 ; metabolism ; Transforming Growth Factor beta1 ; metabolism

OBJECTIVETo investigate the changes of myocardial energy expenditure in patients with heart failure following myocardial infarction after treatment with different doses of perindopril.

METHODSSixty-three patients with heart failure after myocardial infarction were treated with perindopril for 12 months at the doses of 4 mg (group N) and 8 mg (group H). Doppler imaging was used to measure the structural and systolic functional parameters before and after the treatment, and the circumferential end-systolic wall stress (cESS) and myocardial energy expenditure (MEE) were calculated. The biochemical indicators including serum creatinine and plasma NT-proBNP were detected before and after the treatment.

RESULTSThe two groups had similar measurements before treatment. After 12 months of perindopril treatment, the patients in group N showed higher LA, LV, RA, RV, LVIDs, AD, cESS, lgNT-proBNP, and MEE with lower LVFS and LVEF than those in group H. Compared to those before treatment, LVFS and LVEF were increased and LA, LV, RA, RV, AD, LVIDs, LVMI, lgNT-proBNP and MEEm lowered after the 12-month treatment in group H. Significant changes were also found in the measured parameters except for PWTs, LVET, LVSV and LVFS in group N after the treatment. Bivariate analysis showed a significant positive correlation between MEE and lgNT-proBNP (r=0.513, P<0.01).

CONCLUSIONA 12-month treatment with perindopril can suppress myocardial remodeling, improve left ventricular systolic function, and lower NT-proBNP and myocardial energy expenditure in patients with heart failure after myocardial infarction, and a higher dose can produce better results.

Aged ; Energy Metabolism ; Female ; Heart Failure ; drug therapy ; etiology ; metabolism ; Humans ; Male ; Middle Aged ; Myocardial Infarction ; complications ; drug therapy ; Myocardium ; metabolism ; Perindopril ; administration & dosage ; therapeutic use ; Treatment Outcome ; Ventricular Function, Left ; Ventricular Remodeling

OBJECTIVETo study the effects of carvedilol combined with perindopril on Ca(2+) pump activity and the density of Ca(2+)-release channel ryanodine receptor (RyR2) in the myocardial sarcoplasmic reticulum (SR) in rats with chronic heart failure caused by myocardial infarction.

METHODSRat models of chronic heart failure established by left coronary artery ligation were divided into different groups and treated with carvedilol (6 mg.kg(-1).d(-1)), perindopril (4 mg.kg(-1).d(-1)), terazosin (2 mg.kg(-1).d(-1)), or the combination of carvedilol (6 mg.kg(-1).d(-1)) and perindopril (4 mg.kg(-1).d(-1)) for 9 weeks. Another 12 rats with sham operation served as the sham-operated group. The hemodynamic parameters, activity of SR Ca(2+) pump, and RyR2 density were determined.

RESULTSCompared with shame-operated group, the rats with chronic heart failure showed significantly increased left ventricular end-diastolic pressure (LVEDP) (P<0.01) and decreased +dP/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Both monotherapies with carvedilol and perindopril attenuated the increment of LVEDP, and significantly increased +dp/dtmax, -dp/dtmax, activity of SR Ca(2+) pump and density of RyR2 (P<0.01). Combined treatment even further enhanced the therapeutic effects, whereas terazosin produced no obvious effect. The activity of SR Ca(2+) pump was strongly correlated to +dp/dtmax and -dp/dtmax (r=0.596 and 0.684, respectively, P<0.01).

CONCLUSIONProlonged treatment with beta-blocker carvedilol in combination with ACE inhibitor perindopril may improve the hemodynamic parameters, enhance Ca(2+) pump activity and increase the density of RyR2 of myocardial SR more effectively than either monotherapy in preventing and treating chronic heart failure following myocardial infarction.

Animals ; Calcium ; metabolism ; Carbazoles ; pharmacology ; therapeutic use ; Drug Therapy, Combination ; Heart Failure ; drug therapy ; etiology ; metabolism ; Male ; Myocardial Infarction ; complications ; metabolism ; Perindopril ; pharmacology ; therapeutic use ; Propanolamines ; pharmacology ; therapeutic use ; Rats ; Rats, Wistar ; Ryanodine Receptor Calcium Release Channel ; drug effects ; Sarcoplasmic Reticulum ; drug effects ; metabolism

OBJECTIVE: To evaluate the short-term, and long-term therapeutic effects of combination therapy with perindopril and irbesartan in a rat model of dilated cardiomyopathy (DCM). METHODS: Sprague-Dawley rats were administered adriamycin intraperitoneally to develop DCM. Grouping of rats: Group A contained normal rats, and Group B contained DCM rats. Both Group A and B were not given drug treatment. Group C and D contained DCM rats, however, Group C was administered perindopril 2mg/(kg x d) while Group D was administered perindopril 1mg/(kg x d) and irbesartan 25mg/(kg x d). Brain natriuretic peptide (BNP) was determined by enzyme linked immunosorbent assay; plasma potassium and creatinine were measured; the pathological lesions of cardiac muscle tissues were evaluated after HE staining; and the survival time of each rat during the intervention was recorded. RESULTS: After the three-week intervention, the plasma concentrations of BNP in Group D were lower than those in Group C (P<0.05). In each group, plasma concentrations of potassium and creatinine showed no significant differences between pre-intervention and post-intervention (P>0.05); pathological lesions of cardiac muscle tissues in both Group C and D were attenuated compared with those in Group B (P<0.01), but pathological lesions of cardiac muscle tissues showed no significant differences between Group C and Group D (P>0.05). Log-rank test showed that the life span of Group C was shorter than that of Group D (P<0.05); Cox regression analysis showed that both combination therapy and monotherapy with perindopril could prolong the survival time, but the effect of combination therapy was more obvious. CONCLUSION Combination therapy with perindopril and irbesartan in a rat model of DCM can more effectively improve the cardiac function and long-term prognosis than those monotherapy with perindopril. Both these two treatment plans can attenuate the pathological lesions of cardiac muscle tissues, without elevating the concentrations of plasma potassium and creatinine.
Animals ; Biphenyl Compounds ; therapeutic use ; Cardiomyopathy, Dilated ; chemically induced ; drug therapy ; Creatinine ; blood ; Doxorubicin ; adverse effects ; Drug Therapy, Combination ; Irbesartan ; Male ; Myocardium ; pathology ; Natriuretic Peptide, Brain ; metabolism ; Perindopril ; therapeutic use ; Potassium ; blood ; Rats ; Rats, Sprague-Dawley ; Tetrazoles ; therapeutic use ; Treatment Outcome

OBJECTIVEThis study was performed to evaluate whether implantation of mesenchymal stem cell (MSC) would reduce left ventricular remodelling from the molecular mechanisms compared with angiotensin-converting enzyme inhibitors (ACEIs) perindopril into ischemic myocardium after acute myocardial infarction.

METHODSForty rats were divided into four groups: control, MSC, ACEI, MSC+ACEI groups. Bone marrow stem cell derived rat was injected immediately into a zone made ischemic by coronary artery ligation in MSC group and MSC+ACEI group. Phosphate-buffered saline (PBS) was injected into control group. Perindopril was administered p.o. to ACEI group and MSC+ACEI group. Six weeks after implantation, the rats were killed and heart sample was collected. Fibrillar collagen was observed by meliorative Masson's trichome stain. Western Blotting was employed to evaluate the protein expression of matrix metalloproteinase (MMP)-2, matrix metalloproteinase (MMP)-9 in infarction zone. The transcriptional level of MMP2, MMP9 and tissue inhibitor of matrix metalloproteinase (TIMP)-1 in infarction area was detected by reverse transcriptase PCR (RT-PCR) analysis.

RESULTSThe fibrillar collagen area, the protein expression of MMP2, MMP9 and the transcriptional level of MMP2, MMP9 mRNA in infarction zone reduced in MSC group, ACEI group, and MSC+ACEI group. No significant difference was detected in the expression of TIMP1 mRNA among the 4 groups.

CONCLUSIONBoth MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

Angiotensin-Converting Enzyme Inhibitors ; therapeutic use ; Animals ; Bone Marrow Cells ; cytology ; Male ; Matrix Metalloproteinase 2 ; analysis ; Matrix Metalloproteinase 9 ; analysis ; Mesenchymal Stem Cell Transplantation ; Myocardial Infarction ; enzymology ; pathology ; therapy ; Myocardium ; enzymology ; Perindopril ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Tissue Inhibitor of Metalloproteinase-1 ; analysis ; Ventricular Remodeling

OBJECTIVE: To determine the expression and effect of hypoxia-inducible factor 1alpha (HIF-1alpha) in chronic kidney fibrosis, and to observe the effect of perindopril on its expression. METHODS: The rat models of chronic kidney fibrosis were induced by 5/6 nephrectomy, and 11 successful 5/6-nephrectomized rats were randomly assigned to 2 groups: a surgery group (n=6) and a treatment group (perindopril, n=5). A control group was induced by sham operation. Five weeks later, Picro-Sirius red stained was applied to measure collagen in the kidney, and Western blot was used to test HIF-1alpha protein; The expression of HIF-1alpha and CTGF mRNA in the kidney was analyzed by real-time PCR. RESULTS: Picro-Sirius red stained revealed significant accumulation of collagens in the surgery group than the control group; and lower accumulation of collagens in the treatment group than the surgery group. Western blot showed higher deposit HIF-1alpha in the surgery group than the control group (P<0.01) and lower deposit HIF-1alpha in the treatment group than the surgery group (P<0.01). Real time PCR showed higher expression of HIF-1alpha and CTGF mRNA in the surgery group than the control group (P<0.01)and lower expression of HIF-1alpha and CTGF mRNA in kidney of the treatment group compared with the surgery group (P<0.01). The expression of CTGF had positive correlation with HIF-1alpha (r=0.68, P<0.01). CONCLUSION The HIF-1alpha may induce kidney fibrosis through CTGF. Perindopril may decrease the expression of HIF-1alpha and CTGF to ameliorate kidney fibrosis.
Animals ; Connective Tissue Growth Factor ; genetics ; metabolism ; Fibrosis ; metabolism ; Hypoxia-Inducible Factor 1, alpha Subunit ; genetics ; metabolism ; Kidney ; pathology ; Kidney Diseases ; drug therapy ; etiology ; metabolism ; Male ; Nephrectomy ; Perindopril ; pharmacology ; therapeutic use ; RNA, Messenger ; genetics ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley