Single-Arm Clinical Study of Combination Perindopril-Amlodipine Tablets in the Treatment of High-Altitude Hypertension

Objective:To evaluate the efficacy of combination perindopril/amlodipine tablets in patients with high-altitude hypertension who were previously unable to control their blood pressure with monotherapy.Methods:A total of 151 patients with high-altitude hypertension whose blood pressure remained inadequately controlled with previous monotherapy were enrolled in this study.All patients received an 8-week treatment with a combination of perindopril/amlodipine tablets,consisting of perindopril 10 mg/day and amlodipine 5 mg/day.Blood pressure measurements,including both diastolic and systolic pressures,were taken at baseline,and after 2,4,6,and 8 weeks of treatment.Results:After 8 weeks of treatment,there was a significant reduction in both average systolic and diastolic blood pressure compared to baseline(P<0.0001).Specifically,the average systolic blood pressure decreased by 24.45±13.75 mmHg,and the average diastolic blood pressure decreased by 13.37±8.40 mmHg.The overall heart rate showed no significant changes during the treatment period.Conclusion:A combination of perindopril/amlodipine tablets significantly improved blood pressure control in patients with high-altitude hypertension after 8 weeks of treatment.These results support the efficacy of combination perindopril/amlodipine as a viable treatment option for high-altitude hypertension.

Bone marrow mesenchymal stem cell transplantation combined with perindopril treatment attenuates infarction remodelling in a rat model of acute myocardial infarction

Objective: This 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. Methods: Forty 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. Results: The 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. Conclusion: Both MSC and ACEI could reduce infarction remodelling by altering collagen metabolism.

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

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）. lndapamide-d3, perindopril-d4 and perindoprilat-d4 were used as the internal standards. The separation was performed on a Thermo BDS Hypersil C18 column （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 independently 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 perindoprilat. 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.

Angiotensin-converting-enzyme Inhibitors in Treatment of Atherosclerotic Peripheral Arterial Disease

Objective To evaluate the treatment efficacy of perindopril in correcting endothelial dysfunction in patients with atherosclerotic peripheral arterial disease(PAD).Methods 85 patients with atherosclerotic PAD were divided into 3 groups and undergone endotheliotropic treatment with perindopril.The functional state of endothelium(FSE)was evaluated in all patients by checking the following biochemical parameters:nitric oxide(Ⅱ)(NO),endothelin-1(E-1),C-reactive protein(CRP),superoxide dismutase(SOD),integral assessment of lipid peroxidation(LPO),glutathione peroxidase(GPx).Results Basal level of NO secretion in operated patients was the lowest.SOD level in operated patients increased by 102.7%,143.24%,164.86%and 175.67%directly after the operation as well as 1,3 and 6 months following the surgery respectively,but E-1 level decreased by 82%,70%,78%,and 90%.The results of GPx level and LPO analysis confirmed favorable effects of perindopril on biochemical status in patients with atherosclerotic PAD.Conclusion Perindopril is effective in stimulating NO(Ⅱ)secretion and correcting FSE.Perindopril may be used for prophylaxis of restenosis of reconstruction area following operative treatment in patients with atherosclerotic PAD.

Altered angiotensin-converting enzyme and its effects on the brain in a rat model of Alzheimer disease

Background Alzheimer disease （AD） is a neurodegenerative disease related to aging. At present, its pathological mechanisms remain unclear. Family members of the renin-angiotensin system （RAS） play a role in neuronal plasticity, as well as formation of learning and memory. In this study, we explore the effects of altered angiotensin-converting enzyme （ACE）, and investigate the possible mechanisms of perindopril, an ACE inhibitor, on brain structure and function in a rat model of AD, as well as the role that ACE plays in AD. Methods Sixty Sprague-Dawley rats were selected and randomly divided into 3 groups： control, AD, and perindopril. Each group consisted of 20 rats, with 10 rats for determining pathology, and the remaining 10 rats for quantifying ACE activity. The rat AD model was established by stereotactically injecting amyloid beta protein （A-beta） 1-42 into the right hippocampus. Learning and memory functions were tested using the Y-type electric maze. The number and morphology of abnormal neurons were determined by haematoxylin and eosin staining. Amyloid deposition was measured by Congo red staining. Finally, ACE activity was estimated by spectrophotometry. Results Compared with the control group, the number of times needed to escape electrical stimuli increased （23.70±3.13, P 〈0.001）, the number of normal neurons in the CA1 region was reduced （density of 96.5±32.6/mm, P 〈0.001）, amyloid deposition was obvious, and ACE activity increased （（34.4±6.6） nmol.g-1.min-1, P 〈0.001） in the AD group. In the perindopril group, the number of times needed to escape electrical stimuli decreased （18.50±3.66, P 〈0.001）, the number of abnormal neurons increased （density of CA1 neurons was 180.8±28.5/mm, P 〈0.001）, amyloid deposition was reduced, and ACE activity was down-regulated （（26.2±6.2） nmol.g-1.min-1, P 〈0.001）. Conclusions ACE activity increased in the brains of AD rats. Perindopril improved learning and memory in AD rats, which correlated with decreased ACE activity and delayed AD pathogenesis.

A Comparative Study on the Therapeutic Effect of Astragaloside (黄芪总皂甙) and Perindopril in Treating CVB_3-Infected Cardiomyocytes in Rats

Objective: To compare the therapeutic effects of Astragaloside and Perindopril on myocardial sarco/endoplasmic reticulum Ca 2+ ATPase (SERCA) activity and the SERCA type 2 mRNA level in Coxsackievirus B 3 (CVB 3) infected cardiomyocytes. Methods: Cultured cardiomyocytes of rats were divided into normal, model, Astragaloside and Perindopril groups. The model, Astragaloside and Perindopril groups were infected with CVB 3. Meanwhile, the Astragaloside and the Perindopril groups were treated with Astragaloside (10 μg/ml) and Perindopril (1.3 μg/ml) respectively. Cytopathic effect (CPE), cardiac troponin I ( cTnI) , the SERCA activity and mRNA level of the SERCA type 2 were observed after 96 hours. Results: The CPE and cTnI of model group were significantly higher than those of normal, Astragaloside and Perindopril groups ( P <0.01). The activity and the mRNA expression of myocardial SERCA of model group were significantly lower than those of normal, Astragaloside and Perindopril groups ( P <0.01-0.05). Compared with Astragaloside group, the CPE, cTnI of Perindopril group were higher and the activity and mRNA level of Perindopril group were lower. But there were no significant difference between the two groups ( P >0.05). Conclusion: Astragaloside and Perindopril were able to reverse the down regulations of cardiac SERCA activity and mRNA expression caused by virus infection to alleviate the cardiomyocyte injury.

EFFECT OF PERINDOPRIL AND METOPROLOL ON LEFT VENTRICULAR HYPERTROPHY AND PERFORMANCE IN ESSENTIAL HYPERTENSION

The effects of perindopril and metoprolol on left ventricular hypertrophy (LVH) and function were studied in 47 essential hypertensive patients with LVH. Previous antihypertensive drugs were discontinued for at least 2 weeks, after which patients were randomly divided into 2 groups. 25 subjects were treated with perindopril 4 to 8 mg once daily in the morning (Group A) and 22 subjects with metoprolol 25 to 62.5 mg twice daily (Group B). The subjects were evaluated before and after 4 and 8 weeks of treatment by use of echocardiography. Before treatment LV mass indexes (LVMI) of two groups were respectively 143.2 ± 21.3 g / m2 and 140.6 ± 23.7 g / m2 (P>0.05). In Group A, reduction of LVMI occurred after 4 weeks of treatment, and more pronounced after 8 weeks (from 143.2 ± 21.3 g / m2 to 126.6 ± 15.3 g / m2, P< 0.001), whereas reduction of LVMI occurred only after 8 weeks in Group B (from 140.6 ± 23.7 g / m2 to 133.4 ± 13.2 g / m2, P< 0.001). In addition, there was a significant (P<0.05) difference in LVMI between the two groups after 8 weeks. LV systolic function remained unchanged, whereas E / A increased significantly (P< 0.001) in two groups after 8 weeks. In conclusion, antihypertensive treatment with perindopril and metoprolol induced a significant regression of LVH associated with improvement in LV diastolic performance. Perindopril, compared with metoprolol, was more effective in reversing LVH.