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

Calcium channel blockers (CCBs) are very popular drugs to lower blood pressure (BP) without significant side effects. A 72-year-old man admitted for uncontrolled hypertension. He had history of hypertension, atrial fibrillation with slow ventricular response, angina, abdominal aortic aneurysm, and stage 3 chronic kidney disease. He had taken several anti-hypertensives, such as amlodipine 5 mg, perindopril 8 mg, and indepamide 1.5 mg. To control BP, nifedipine 120 mg was added. Then pulmonary edema and pleural effusion was developed. Echocardiography showed preserved left ventricular ejection fraction and mild mitral regurgitation. Fluid restriction and high dose furosemide did not cease pleural fluid accumulation. Thus a total of 4 times of thoracentesis were done and all fluid analyses revealed transudate. We thought that pleural effusion and pulmonary edema was induced by CCBs and discontinued the drugs. He recovered quickly and finally discharged in a stable condition.
Aged ; Amlodipine ; Antihypertensive Agents ; Aortic Aneurysm, Abdominal ; Atrial Fibrillation ; Blood Pressure ; Calcium Channel Blockers* ; Calcium Channels* ; Calcium* ; Echocardiography ; Exudates and Transudates ; Furosemide ; Humans ; Hypertension* ; Mitral Valve Insufficiency ; Nifedipine ; Perindopril ; Pleural Effusion* ; Pulmonary Edema* ; Renal Insufficiency, Chronic ; Stroke Volume

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 investigate the expression of Toll-like receptor 4 (TLR4) in the liver tissue of rats with bile duct ligation (BDL)-induced hepatic fibrosis and evaluate the inhibitory effects of perindopril and losartan on TLR4 expression.

METHODSMale Wistar Rats were randomly divided into sham-operated group (n=6), BDL group, perindopril treatment group (2 mg/kg) and losartan treatment group (50 mg/kg) (n=12). Perindopril and losartan groups were further divided into two subgroups for corresponding treatments by gastric lavage once daily for 14 and 30 days. The protein level of TLR4 in the liver tissue was examined by Western blotting.

RESULTSIn 14-day BDL group, the protein level of TLR4 significantly increased to 6.53∓1.11 folds of that in the sham group (P<0.05), and was lowered significantly to 1.71∓0.41 folds and 0.95∓0.38 folds following perindopril and losartan treatments for 14 days. TLR4 expression significantly increased to 6.51∓0.87 folds and 5.64∓0.87 folds of that of the sham group in perindopril and losartan groups after the 30-day treatments (P<0.05).

CONCLUSIONTLR4 expression is up-regulated in the liver of rats with BDL-induced hepatic fibrosis, and can be lowered by perindopril and losartan treatmemts for 14 days.

Animals ; Bile Ducts ; surgery ; Down-Regulation ; drug effects ; Ligation ; Liver Cirrhosis, Experimental ; metabolism ; pathology ; Losartan ; pharmacology ; Male ; Perindopril ; pharmacology ; Rats ; Rats, Wistar ; Toll-Like Receptor 4 ; genetics ; 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

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.
Blood Glucose ; Cardiovascular Diseases ; Consensus ; Diabetes Complications ; Diabetes Mellitus ; Drug Combinations ; Gliclazide ; Glucose ; Humans ; Indapamide ; Perindopril ; Solar System ; Veterans

A conference was convened by the Korean Diabetes Association and the Korean Endocrine Society on September 7, 2009 to discuss and organize the results of research on intensive glucose control for the prevention of cardiovascular disease in patients with type 2 diabetes. Professor Kyung Soo Park led the conference, and Professors Kwang Won Kim and Ho Young Son acted as chairmen. Professors Doo Man Kim, Tae Sun Park, and Bong Soo Cha reported on intensive glucose control and diabetic complications, including the UK Prospective Diabetes Study (UKPDS), Diabetes Control and Complication Trial (DCCT) research results, the recently published Action to Control Cardiovascular Risk in Diabetes (ACCORD), Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE), and Veterans Affairs Diabetes Trial (VADT) research, as well as meta-analyses. Professor Jeong-Taek Woo reported on the manuscript written by the committee for the Korean Diabetes Association which dealt with the treatment of diabetes mellitus. Professors Kyung Soo Ko, Joong Yeol Park, Hyun Shik Son, Moon-Kyu Lee, Dong-Won Byun, and Yoon-Sok Chung participated in the discussion and collected information for the manuscript from all of the participants. The aim of the debate was to determine how to establish target goals for intensive glucose control and how to individualize those goals. The participants concluded that there was no need to modify the recommendation of maintaining an HbA1c under 6.5%, the current blood glucose treatment goal that is recommended by the Korean Diabetes Association. In addition, individual target goals for glucose control were recommended depending on the situation of each patient. We report on the consensus statement from the meeting.
Blood Glucose ; Cardiovascular Diseases ; Consensus ; Diabetes Complications ; Diabetes Mellitus ; Drug Combinations ; Gliclazide ; Glucose ; Humans ; Indapamide ; Perindopril ; Solar System ; Veterans

BACKGROUND: The aim of this study was to investigate the relations between arterial stiffness, diastolic function, and exercise performance and the effects of angiotensin-converting enzyme inhibitor(ACEI), perindopril, in these three areas in patients with hypertension(HT). METHODS: A total of 39 patients(60.9+/-4.9 years, 23 males) with a newly diagnosed or untreated HT, stage I, were enrolled. Arterial stiffness measured by pulse wave velocity, diastolic function measured by echocardiography, and exercise performance and hemodynamic parameters measured by a treadmill exercise test were compared before and after 6 months of medical treatment with an ACEI. RESULTS: The parameters for arterial stiffness, diastolic function, and exercise performance did not show significant correlations with each other at baseline. Systolic(from 147.6+/-6.5mmHg to 134.3+/-9.6mmHg, p<0.001) and diastolic blood pressures(from 87.7+/-7.5mmHg to 82.9+/-6.2mmHg, p<0.001) decreased significantly after 6 months of ACEI treatment. Except for duration of total exercise time, the parameters for arterial stiffness, diastolic function, and the hemodynamic response to exercise also improved significantly after 6 months of ACEI treatment. CONCLUSION: Though the parameters for arterial stiffness, diastolic function, and exercise performance were not asso- ciated with each other at baseline, they all improved significantly after 6 months of medical treatment with an ACEI in elderly patients with stage I HT. The results of this study suggest the possibility of additional benefits of ACEI beyond lowering blood pressure.
Aged ; Echocardiography ; Exercise Test ; Hemodynamics ; Humans ; Perindopril ; Pulse Wave Analysis ; Vascular Stiffness

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 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