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Cells Mar 2021(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible...
(1) Background: Recently, influences of antihypertensive treatment on the renin-angiotensin-aldosterone system (RAAS) has gained attention, regarding a possible influence on inflammatory and anti-inflammatory pathways. We aimed to study the effects of newly initiated antihypertensive drugs on angiotensin (Ang) II and Ang (1-7) as representers of two counter-regulatory axes. (2) Methods: In this randomized, open-label trial investigating RAAS peptides after the initiation of perindopril, olmesartan, amlodipine, or hydrochlorothiazide, Ang II and Ang (1-7) equilibrium concentrations were measured at 8 a.m. and 12 a.m. at baseline and after four weeks of treatment. Eighty patients were randomized (1:1:1:1 fashion). (3) Results: Between the four substances, we found significant differences regarding the concentrations of Ang II ( < 0.0005 for 8 a.m., 12 a.m.) and Ang (1-7) ( = 0.019 for 8 a.m., <0.0005 for 12 a.m.) four weeks after treatment start. Ang II was decreased by perindopril ( = 0.002), and increased by olmesartan ( < 0.0005), amlodipine ( = 0.012), and hydrochlorothiazide ( = 0.001). Ang (1-7) was increased by perindopril and olmesartan ( = 0.008/0.002), but not measurably altered by amlodipine and hydrochlorothiazide ( = 0.317/ 0.109). (4) Conclusion: The initiation of all first line antihypertensive treatments causes early and distinct alterations of equilibrium angiotensin levels. Given the additional AT1R blocking action of olmesartan, RAAS peptides shift upon initiation of perindopril and olmesartan appear to work in favor of the anti-inflammatory axis compared to amlodipine and hydrochlorothiazide.
Topics: Antihypertensive Agents; Female; Humans; Hypertension; Male; Middle Aged; Renin-Angiotensin System
PubMed: 33802464
DOI: 10.3390/cells10030534 -
Biomedicine & Pharmacotherapy =... Feb 2024Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It... (Review)
Review
Telmisartan is an antagonist of the angiotensin II receptor used in the management of hypertension (alone or in combination with other antihypertensive agents. It belongs to the drug class of angiotensin II receptor blockers (ARBs). Among drugs of this class, telmisartan shows particular pharmacologic properties, including a longer half-life than any other angiotensin II receptor blockers that bring higher and persistent antihypertensive activity. In hypertensive patients, telmisartan has superior efficacy than other antihypertensive drugs (losartan, valsartan, ramipril, atenolol, and perindopril) in controlling blood pressure, especially towards the end of the dosing interval. Telmisartan has a partial PPARγ-agonistic effect whilst does not have the safety concerns of full agonists of PPARγ receptors (thiazolidinediones). Moreover, telmisartan has an agonist activity on PPARα and PPARδ receptors and modulates the adipokine levels. Thus, telmisartan could be considered as a suitable alternative option, with multi-benefit for all components of metabolic syndrome including hypertension, diabetes mellitus, obesity, and hyperlipidemia. This review will highlight the role of telmisartan in metabolic syndrome and the main mechanisms of action of telmisartan are discussed and summarized. Many studies have demonstrated the useful properties of telmisartan in the prevention and improving of metabolic syndrome and this well-tolerated drug can be greatly proposed in the treatment of different components of metabolic syndrome. However, larger and long-duration studies are needed to confirm these findings in long-term observational studies and prospective trials and to determine the optimum dose of telmisartan in metabolic syndrome.
Topics: Humans; Telmisartan; Angiotensin Receptor Antagonists; Metabolic Syndrome; PPAR gamma; Prospective Studies; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Hypertension; Antihypertensive Agents; Blood Pressure; Benzoates
PubMed: 38228033
DOI: 10.1016/j.biopha.2024.116169 -
Advances in Therapy Jun 2023This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina... (Observational Study)
Observational Study
Effectiveness and Tolerability of Bisoprolol/Perindopril Single-Pill Combination in Patients with Arterial Hypertension and a History of Myocardial Infarction: The PRIDE Observational Study.
INTRODUCTION
This study assessed the real-life effectiveness of a single-pill combination (SPC) of bisoprolol/perindopril for controlling blood pressure (BP) and symptoms of angina in patients with hypertension and a history of myocardial infarction (MI).
METHODS
Eligible patients with arterial hypertension and a history of MI were aged 18-79 years and had initiated bisoprolol/perindopril SPC within 3 months of study enrollment as part of routine Russian clinical practice. The primary endpoint was mean change in systolic and diastolic BP (SBP/DBP) at week 12 compared with baseline (data collected retrospectively). Secondary endpoints were assessed at weeks 4 and 12 and included mean change in resting heart rate (HR), proportion of patients reaching target level of resting HR, antianginal effectiveness of the SPC, and proportion of patients reaching target BP levels.
RESULTS
A total of 504 patients were enrolled, of whom 481 comprised the full analysis set (mean age 61.4 ± 8.9 years, 68% men). Mean baseline SBP/DBP and HR values were 148.9 ± 16.8/87.7 ± 11.0 mmHg and 77.4 ± 10.5 bpm, respectively. Mean durations of hypertension and CAD were 12.8 ± 8.4 and 6.1 ± 6.3 years, respectively, and time since MI was 3.8 ± 5.3 years. At week 12, SBP/DBP had decreased by 24.9/12.2 mmHg (P < 0.001 vs baseline). Target BP (< 140/90 mmHg) was achieved by 69.8% and 95.9% of patients at weeks 4 and 12, respectively, and target HR (55-60 bpm) by 17.3% and 34.5% at weeks 4 and 12 versus 3.1% at baseline (P < 0.001). Reductions in angina attacks, nitrate consumption, and improvements in HR were statistically significant. Treatment was well tolerated.
CONCLUSION
Treatment of symptomatic patients with CAD, hypertension, and a history of MI with a bisoprolol/perindopril SPC was associated with significant decreases in SBP/DBP and a high proportion of patients achieving BP treatment goals. This was accompanied by improvements in angina symptoms and reductions in HR in a broad patient population representative of those seen in everyday clinical practice.
TRIAL REGISTRATION
ClinicalTrials.gov Identifier NCT04656847.
Topics: Male; Humans; Middle Aged; Aged; Female; Perindopril; Bisoprolol; Antihypertensive Agents; Retrospective Studies; Hypertension; Blood Pressure; Myocardial Infarction; Angina Pectoris; Drug Combinations; Treatment Outcome
PubMed: 37029871
DOI: 10.1007/s12325-023-02462-9 -
Combination therapy in the extended cardiovascular continuum: a focus on perindopril and amlodipine.Journal of Cardiovascular Medicine... May 2015The progression of cardiovascular disease could be regarded as following atherosclerosis-related and age-related pathways. The starting points for these pathways are... (Review)
Review
The progression of cardiovascular disease could be regarded as following atherosclerosis-related and age-related pathways. The starting points for these pathways are different--risk factors or aortic ageing--but they conclude in the same way: end-stage heart disease. Together these interlinked pathways form the extended cardiovascular continuum. Renin-angiotensin-aldosterone system (RAAS) inhibitors have been shown to interrupt or slow the progression of cardiovascular disease along one pathway, the cardiovascular atherosclerotic continuum. Cardiovascular protection with RAAS inhibitors varies; different RAAS inhibitors offer different levels of protection. Similarly, calcium channel blockers (CCBs) also have clearly shown protective effect of cardiovascular system, especially as it regards cerebrovascular disease risk. The AngloScandinavian Cardiac Outcomes Trial (ASCOT) showed that a combination of the angiotensin-converting enzyme (ACE) inhibitor perindopril and CCB amlodipine offered better cardiovascular protection in at-risk hypertensive patients than beta-blocker and thiazide. By attenuating the deleterious effects of cardiovascular disease at multiple stages of the extended cardiovascular continuum on top of lowering blood pressure (BP), perindopril and amlodipine could interrupt and slow the progression of cardiovascular disease. These antihypertensive agents have complementary vascular effects that enhance cardiovascular protection and reduce side-effects. Evidence from ASCOT shows that antihypertensive and vascular effects of amlodipine with and without perindopril have translated into real-life clinical benefits. A strategy using ACE inhibitors and CCBs, such as perindopril and amlodipine, to target multiple stages in both pathways of cardiovascular disease could effectively reduce cardiovascular risk and lower BP.
Topics: Amlodipine; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Calcium Channel Blockers; Cardiovascular Diseases; Disease Progression; Drug Combinations; Humans; Hypertension; Perindopril
PubMed: 25590639
DOI: 10.2459/JCM.0000000000000240 -
Frontiers in Physiology 2019Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3...
Ventricular remodeling is considered the basis of heart failure and is involved in myocardial fibrosis. This study aimed to assess perindopril and a galectin-3 inhibitor (modified citrus pectin, MCP) for their effects on ventricular remodeling and myocardial fibrosis in rabbits with ischemic heart failure. Rabbits were divided into sham, heart failure (model), MCP, and perindopril groups, respectively. A rabbit model of ischemic heart failure was established by ligating the anterior descending coronary artery. Then, the rabbits were orally administered MCP, perindopril, or saline (all at 2 ml/kg/d) for 4 weeks. Sham animals only underwent open heart surgery without further treatment. After 4 weeks, cardiac function was examined by ultrasound, and myocardial Gal-3, collagen type I, and collagen type III expression was assessed, at the gene and protein levels, by real-time PCR and Western-Blot, respectively; serum Gal-3 was detected by ELISA, and fibrosis in the infarct zone was evaluated by H&E and Masson staining. In model animals, myocardial Gal-3, collagen type I, and collagen type III gene and protein expression levels were increased compared with control values, as well as serum Gal-3 amounts. Treatment with perindopril and MCP significantly alleviated the above effects, with no significant differences between the treatment groups. Pathological analyses showed that compared with model animals, treatment with MCP or perindopril resulted in relatively neatly arranged myocardial cells in the infarct zone, with significantly decreased fibrosis. Perindopril and the galectin-3 inhibitor MCP comparably improve ischemic heart failure in rabbits, by downregulating Gal-3 and reducing myocardial fibrosis.
PubMed: 30967790
DOI: 10.3389/fphys.2019.00267 -
Cellular Physiology and Biochemistry :... 2018Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded...
BACKGROUND/AIMS
Recent studies indicate that therapies targeting the vasculature can significantly sensitize tumors to radiation. Ultrasound-stimulated microbubbles (USMBs) are regarded as a promising radiosensitizer. In this study, we investigated the effect of USMBs on the sensitivity of nasopharyngeal carcinoma (NPC) to radiation.
METHODS
Human NPC (CNE-2) cells and human umbilical vein endothelial cells (HUVECs) were exposed to radiation (0, 2, and 8 Gy) alone or in combination with USMBs. Cell viability and apoptosis were measured with the MTT assay and flow cytometry, respectively. The angiogenic activity of HUVECs was detected using matrigel tubule formation. The in vitro effects induced by these treatments were confirmed in vivo with xenograft models of CNE-2 cells in nude mice by examining vascular integrity using color Doppler flow imaging and cell survival using immunohistochemistry. Additionally, the in vivo and in vitro expressions of angiotensin II (ANG II) and its receptor (AT1R) were detected by immunohistochemistry and western blotting, respectively. With CNE-2 cells and HUVECs transfected with control, ANG II, or AT1R, perindopril (an inhibitor of angiotensin-converting enzyme) and candesartan (an inhibitor of AT1R) were used to verify the role of ANG II and AT1R in the radiosensitivity of tumor and endothelial cells by USMBs, by determining cell viability and apoptosis and angiogenic activity.
RESULTS
In the NPC xenografts, USMBs slightly reduced blood flow and CD34 expression, increased tumor cell death and ANG II and AT1R expression, and significantly enhanced the effects of radiation. With CNE-2 cells and HUVECs, the USMBs further enhanced the inhibition of tumor cell viability and endothelial tubule formation and further enhanced the increase in ANG II and AT1R due to radiation. Furthermore, perindopril and candesartan significantly enhanced the inhibitory effect of radiation and USMBs on tumor cell growth and angiogenesis in vitro.
CONCLUSIONS
We have demonstrated for the first time that USMB exposure can significantly enhance the destructive effect on NPC of radiation, and this effect might be further increased by ANG II and AT1R inhibition. Our findings suggest that USMBs can be used as a promising sensitizer of radiotherapy to treat NPC, and the clinical effect might be increased by ANG II and AT1R inhibition.
Topics: Angiotensin II; Animals; Antigens, CD34; Benzimidazoles; Biphenyl Compounds; Carcinoma; Cell Line, Tumor; Cell Proliferation; Cell Survival; Contrast Media; Female; Gamma Rays; Human Umbilical Vein Endothelial Cells; Humans; Mice; Mice, Nude; Microbubbles; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Perindopril; Receptor, Angiotensin, Type 1; Sonication; Tetrazoles
PubMed: 30071515
DOI: 10.1159/000492263 -
Evidence-based Complementary and... 2022Chronic kidney disease (CKD) is a major public health problem worldwide. Treatment with renin-angiotensin system inhibitors can achieve only partial efficacy on renal...
BACKGROUND
Chronic kidney disease (CKD) is a major public health problem worldwide. Treatment with renin-angiotensin system inhibitors can achieve only partial efficacy on renal function decline and renal fibrosis in CKD patients. Huangqi-Danshen decoction (HDD) is a basic Chinese herbal pair which is commonly used to treat CKD with good efficacy.
OBJECTIVES
The current study aimed to investigate the effect of perindopril erbumine (PE), an angiotensin-converting enzyme inhibitor, combined with HDD on adenine-induced CKD rat model and explore the possible mechanism from Sirtuin3/mitochondrial dynamics pathway.
METHOD
CKD rat model was established by feeding of 0.75% w/w adenine containing diet for 3 weeks. At the same time, the treatment groups were given PE (0.42 mg/kg/d) or HDD (4.7 g/kg/d) or PE combined with HDD by gavage for 4 weeks. Renal function was evaluated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). The renal pathological injury was observed by periodic acid-Schiff (PAS) and Masson's trichrome staining. Proteins expression was determined by Western blot analysis. Mitochondrial morphology was observed by transmission electron microscopy.
RESULTS
PE in combination with HDD significantly improved renal function, reduced tubular injury and interstitial fibrosis in adenine-induced CKD rats. Moreover, PE + HDD treatment mainly activated the Sirtuin3 expression level. In addition, PE + HDD exhibited bidirectional regulation on mitochondrial dynamics by suppressing mitochondrial fission protein dynaminrelated protein 1 expression and elevating mitochondrial fusion protein optic atrophy 1 expression, resulted in restraint of mitochondrial fragmentation.
CONCLUSION
The combination of PE and HDD attenuated adenine-induced CKD in rats, which was possibly associated with Sirtuin3/mitochondrial dynamics pathway.
PubMed: 35677375
DOI: 10.1155/2022/5812105 -
BMC Chemistry Jun 2023In addition to its pure form, three accurate, rapid, and simple methods have been established for determining perindopril (PRD) in its tablet form. At pH 9.0 using a...
In addition to its pure form, three accurate, rapid, and simple methods have been established for determining perindopril (PRD) in its tablet form. At pH 9.0 using a borate buffer, developing the three designated methods was successful according to the reaction between PRD and 4-chloro-7-nitrobenzo-2-oxa-1,3-diazole (NBD-Cl) and the formation of a chromogen (with a yellow color) measurable at 460 nm using the spectrophotometric method (Method I). In addition, the produced chromogen was assessed using the spectrofluorimetric method (Method II) at 535 nm following excitation at 461 nm. Afterward, the same reaction product was separated and determined using the HPLC method with fluorescence detection (Method III). A Promosil C stainless steel column (Q7 5 mm particle size, 250-4.6 mm) has proven suitable for separation. The mobile phase adjustment was made at pH 3.0, with a 1.0 mL min flow rate; its composition was methanol-sodium dihydrogen phosphate, 0.02 M (60: 40, v/v). Through concentration ranges of 5.0-60.0, 0.5-6.0, and 1.0-10.0 μg mL, the calibration curves were rectilinear for Methods I, II, and III, respectively, with limits of quantification (LOQ) of 1.08, 0.16 and 0.19 μg mL as well as limits of detection (LOD) of 0.36, 0.05 and 0.06 μg mL. The developed methods were implemented to estimate PRD in tablets, and a comparison between the obtained outcomes utilizing the developed methods as well as obtained from the official method revealed that they were comparable. The official BP method was based on dissolving PRD in anhydrous acetic acid and titrating with 0.1 M perchloric acid, then the potentiometric determination of the end-point. The designated methods were also implemented in content uniformity testing with satisfying results. The reaction pathway proposal was speculated, and according to ICH Guidelines, the statistical evaluation of the data was performed. The three proposed methods were confirmed to be green, eco-friendly and safe to environment using Green Analytical procedure index (GAPI) method.
PubMed: 37349827
DOI: 10.1186/s13065-023-00964-9 -
Drug Design, Development and Therapy 2020This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma... (Observational Study)
Observational Study
OBJECTIVE
This study aimed to quantify the amount of perindopril and its active metabolite perindoprilat present in breast milk and corresponding maternal and infant plasma concentrations.
DESIGN
Prospective, longitudinal, observational.
SETTING
Tertiary specialist paediatric and obstetric hospital in Adelaide, South Australia.
POPULATION
Breastfeeding women actively treated with perindopril for hypertensive disorders postpartum.
METHODS
Eight breast milk samples and a single plasma sample were collected from each participant over a 24 hrs period, and plasma samples were taken from eligible breastfed infants. Breast milk and plasma concentrations of perindopril and perindoprilat were analysed using a validated Liquid Chromatography tandem-Mass Spectrometry (LC-MS/MS) method.
MAIN OUTCOME MEASURES
Mean breast milk concentrations of perindopril and perindoprilat, Relative Infant Dose (RID) <10%, and Theoretical Infant Dose (TID).
RESULTS
Ten women and three infants participated in the study. The mean concentration of perindopril in breast milk for each participant ranged from 0.003 to 1.2 ng/mL and perindoprilat 0.2-36 ng/mL. RID for perindopril was 0.0005-0.2% and perindoprilat 0.03-4.6%. TID for perindopril was 0.00045-0.18 µg/kg/day and perindoprilat 0.032-5.4 µg/kg/day. Infant plasma levels for perindopril ranged from 0.44 to 1.12 ng/mL and perindoprilat undetectable - 10.14 ng/mL. Maternal reports described normal infant growth and development.
CONCLUSION
Infant exposure to perindopril and perindoprilat through breast milk is low. However, some infants were found to have plasma perindoprilat concentrations consistent with pharmacodynamic effects. Perindopril may be used in mothers of healthy term infants, provided the infant is carefully monitored.
Topics: Adult; Angiotensin-Converting Enzyme Inhibitors; Breast Feeding; Female; Humans; Indoles; Infant; Male; Middle Aged; Milk, Human; Perindopril; Prospective Studies; Young Adult
PubMed: 32184565
DOI: 10.2147/DDDT.S239704 -
Heliyon Feb 2022Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role...
Alzheimer's disease (AD) is a common neurodegenerative disorder. Aluminium chloride induces AD like pathology in rats. Renin angiotensin system plays a significant role in the pathogenesis and occurrence of Alzheimer's disease. In the present study we evaluated and compared the effect of Captopril and Perindopril against aluminium chloride induced amyloidogenesis and cognitive dysfunction in rats. Wistar rats of both sex were divided randomly into four groups i.e. Group I was served as normal control and treated with normal saline, Group II was administered with AlCl (100 mg/kg, p. o.) and Group III and IV received Captopril (30 mg/kg, p. o.) and Perindopril (5 mg/kg, p. o.) respectively 1hr prior to administration of AlCl. All the doses were given once daily for 42 days. The evaluation of memory function was carried out in Y-maze (spontaneous alternation), radial arm maze (number of correct responses) and elevated plus maze (transfer latency). After behavioral studies, estimation of antioxidant status (brain and serum), amyloid-β content (brain) and histopathology of brain hippocampus region was done. Administration of AlCl for 42 days impaired cognitive dysfunction. Captopril and Perindopril prevented AlCl induced cognitive dysfunction by improving spontaneous alternation behavior, number of correct responses and reducing transfer latency. They also increase the antioxidant status, reduce the Aβ42 content in the brain and reverse the histopathological changes caused by AlCl in hippocampal region. Both Captopril and Perindopril protects against aluminium chloride induced amyloidogenesis and AD like pathology. Captopril is found to be more effective than Perindopril.
PubMed: 35243060
DOI: 10.1016/j.heliyon.2022.e08935