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Cardiology Research and Practice 2022Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are...
BACKGROUND
Some antihypertensive medications alter cellular energy production, presumably by modification of the mitochondrial function. In vivo studies of such effects are challenging in humans. We applied a noninvasive forearm skin measurement of the 460-nm fluorescence specific for the reduced form of nicotinamide adenine dinucleotide (NADH) to study the 6-week effects of four different antihypertensive medications on mitochondrial function using the Flow-Mediated Skin Fluorescence (FMSF).
METHODS
In a prospective open-label study, we compared the long-term effects of a 6-week treatment with either amlodipine (5 mg), perindopril (5 mg), nebivolol (5 mg), or metoprolol (50 mg) on the dynamic flow-mediated changes in the skin NADH content in 76 patients (29 women) with untreated primary arterial hypertension (HA). Patients underwent 24-hour ambulatory blood pressure monitoring. To study mitochondrial function, the FMSF was measured at rest, during 100-second ischemia and postischemic reperfusion. The control group consisted of 18 healthy people (7 women).
RESULTS
There were no significant differences in the FMSF parameters between the control and the study group before medication. After the 6-week treatment, all drugs similarly reduced blood pressure. Neither amlodipine, perindopril, nor nebivolol changed the flow-mediated 460-nm skin fluorescence significantly. However, metoprolol raised this fluorescence at rest, during ischemia and reperfusion ( at most <0.05), indicating an increase in the total NADH skin content.
CONCLUSION
Amlodipine, perindopril, and nebivolol appear neutral for the skin NADH content during the 6-week antihypertensive treatment. Similar treatment with metoprolol increased skin NADH at rest, during ischemia and reperfusion, probably due to an effect on microcirculation and altered mitochondrial function. Explanation of the potential mechanisms behind metoprolol influence on the skin NADH metabolism requires further investigation.
PubMed: 35402043
DOI: 10.1155/2022/6159883 -
American Journal of Cardiovascular... May 2022
PubMed: 35352322
DOI: 10.1007/s40256-022-00535-8 -
Oxidative Medicine and Cellular... 2022Duchenne muscular dystrophy involves an absence of dystrophin, a cytoskeletal protein which supports cell structural integrity and scaffolding for signalling molecules...
Duchenne muscular dystrophy involves an absence of dystrophin, a cytoskeletal protein which supports cell structural integrity and scaffolding for signalling molecules in myocytes. Affected individuals experience progressive muscle degeneration that leads to irreversible loss of ambulation and respiratory diaphragm function. Although clinical management has greatly advanced, heart failure due to myocardial cell loss and fibrosis remains the major cause of death. We examined cardiac morphology and function in D2.B10-Dmd /J (D2-) mice, a relatively new mouse model of muscular dystrophy, which we compared to their wild-type background DBA/2J mice (DBA/2). We also tested whether drug treatment with a specific blocker of mitochondrial permeability transition pore opening (Debio-025), or ACE inhibition (Perindopril), had any effect on dystrophy-related cardiomyopathy. D2- mice were treated for six weeks with Vehicle control, Debio-025 (20 mg/kg/day), Perindopril (2 mg/kg/day), or a combination ( = 8/group). At 18 weeks, compared to DBA/2, D2- hearts displayed greater ventricular collagen, lower cell density, greater cell diameter, and greater protein expression levels of IL-6, TLR4, BAX/Bcl2, caspase-3, PGC-1, and notably monoamine oxidases A and B. Remarkably, these adaptations in D2- mice were associated with preserved resting left ventricular function similar to DBA/2 mice. Compared to vehicle, although Perindopril partly attenuated the increase in heart weight and collagen at 18 weeks, the drug treatments had no marked impact on dystrophic cardiomyopathy.
Topics: Animals; Cardiomyopathies; Dystrophin; Fibrosis; Mice; Mice, Inbred DBA; Mice, Inbred mdx; Muscular Dystrophy, Duchenne; Myocytes, Cardiac; Ventricular Function, Left
PubMed: 35340200
DOI: 10.1155/2022/5362115 -
Evidence-based Complementary and... 2022Myocardial fibrosis caused by myocardial infarction (MI) is the key factor leading to cardiac remodeling; nod-like receptor family pyrin domain-containing 3 (NLRP3)...
BACKGROUND
Myocardial fibrosis caused by myocardial infarction (MI) is the key factor leading to cardiac remodeling; nod-like receptor family pyrin domain-containing 3 (NLRP3) plays an important role in regulation of myocardial injury; however, its relationship with TLR4/MyD88/NF-B signaling pathway is largely unreported. In recent years, traditional Chinese medicine (TCM) prevention and treatment of cardiovascular diseases has shown its unique advantages and broad application prospects. LuQi Formula (LQF) has been used for more than 20 years in Shuguang Hospital (Shanghai, China), and it was confirmed that it can improve the clinical symptoms of patients after MI. Here, we investigated the mechanism of LQF by suppressing NLRP3 inflammasome activation and TLR4/MyD88/NF-B pathway in mice with MI.
PURPOSE
The purpose of this study was to verify the positive effects of the LQF in ameliorating myocardial fibrosis and inflammasome infiltration in the MI mice in vivo.
METHODS
Forty mice were randomized into four groups: the sham group, the MI group, the LQF group, and the perindopril group ( = 10 per group). Left anterior descending (LAD) coronary artery ligation was performed in all groups except the sham group. The mice were treated with LQF after MI. After 4 weeks, LDH, cTnI, IL-1, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) kit, and cardiac function was evaluated by echocardiography. Hematoxylin and eosin (H&E) and Masson staining were used to evaluate the myocardial injury and fibrosis. Western blot was used to evaluate the expression of collagen I, -SMA, NLRP3 inflammasome, and TLR4/MyD88/NF-B signaling pathway. Immunohistochemical analysis was used to further detect the expression of Fibronectin, -SMA, collagen I, collagen III, NLRP3, and NF-B in myocardial tissue.
RESULTS
Compared with the MI group, the ejection fraction (EF) and fractional shortening (FS) in the LQF group were significantly improved, while the left ventricular end diastolic diameter (LVEDd) and left ventricular internal dimension systole (LVIDs) were significantly decreased. The representative staining of H&E and Masson showed that treatment with LQF could effectively reduce myocardial injury and fibrosis. ELISA results showed that serum LDH, cTnI, TNF-, IL-18, and IL-1 in LQF group were significantly lower than those in MI group. The western blot results showed that the expressions of collagen I and -SMA were decreased significantly in the LQF group. Moreover, the expressions of NLRP3 inflammasome and TLR4/MyD88/NF-B signaling pathway were downregulated in the LQF treatment group.
CONCLUSION
Our results suggested that LQF could significantly improve cardiac function and ameliorate myocardial fibrosis. In addition, we found that LQF could downregulate the TLR4/MyD88/NF-B signaling pathway and then inhibit the activation of NLRP3 inflammasome, suggesting that LQF alleviated cardiac fibrosis by decreasing the TLR4/MyD88/NF-B signaling pathway and then inhibited NLRP3 inflammasome activation in MI mice, which indicates potential therapeutic effect of LQF on patients with MI.
PubMed: 35310035
DOI: 10.1155/2022/5867987 -
American Journal of Cardiovascular... Mar 2022The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension... (Review)
Review
The single-pill combination (SPC) of perindopril (PER)/indapamide (IND)/amlodipine (AML) is a valuable and convenient treatment option for patients with hypertension controlled with two-drug SPC of PER/IND + AML given as two separate pills at the same dose level. PER [an angiotensin-converting enzyme (ACE) inhibitor], IND (a thiazide-like diuretic) and AML (a calcium channel blocker) are well established antihypertensive agents, which have been available for a long time as monotherapies and dual SPCs and have complementary mechanisms of action. Once-daily PER/IND/AML provided effective BP control, with good tolerability, in patients with uncontrolled hypertension in clinical trials and in large observational prospective studies. The efficacy and tolerability of PER/IND/AML was similar to that of PER/IND + AML in a randomized clinical trial. The therapeutic effect of PER/IND/AML was associated with improved health-related quality of life. Thus, switching from the two-pill PER/IND + AML regimen to single-pill PER/IND/AML reduces pill burden and simplifies drug administration, which may improve adherence to treatment, leading to better BP control and clinical outcomes.
Topics: Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Humans; Hypertension; Indapamide; Perindopril; Prospective Studies; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 35257306
DOI: 10.1007/s40256-022-00521-0 -
BMC Cardiovascular Disorders Mar 2022This study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in outpatients with uncontrolled isolated systolic... (Observational Study)
Observational Study
BACKGROUND
This study evaluated the effectiveness of treatment with an indapamide/amlodipine single-pill combination (SPC) in outpatients with uncontrolled isolated systolic hypertension (ISH) aged over 55 years in real-life clinical practice.
METHODS
This was a post-hoc analysis of the subgroup of patients with ISH from ARBALET, a 3-month, multicenter, observational, open-label study conducted in Russia among patients with grade I or II hypertension who were either uncontrolled on previous antihypertensive treatment or treatment-naïve. The effectiveness of indapamide/amlodipine SPC was assessed by the change in office systolic blood pressure (SBP) and the rate of target SBP (< 140 mmHg) achievement at 2 weeks, 1 month and 3 months, in four age groups: 55-59 years, 60-69 years, 70-79 years, and 80 years or older.
RESULTS
The ARBALET study recruited 2217 patients, of whom 626 had ISH and were included in this post-hoc analysis (mean age 66.1 ± 7.8 years; 165 men [26.4%] and 461 women [73.6%]). Target SBP < 140 mmHg was achieved in 43%, 75% and 93% of patients at 2 weeks, 1 and 3 months, respectively. SBP decreased from baseline by 18.8 ± 10.5 mmHg, 27.2 ± 10.6 mmHg and 31.8 ± 9.9 mmHg at 2 weeks, 1 month and 3 months, respectively. In the groups of patients aged 55-59, 60-69, 70-79, and ≥ 80 years, SBP reductions at 3 months compared with baseline were - 30.3 ± 9.4, - 32.4 ± 9.7, - 32.5 ± 10.7, and - 28.9 ± 9.6 mmHg, respectively.
CONCLUSION
This post-hoc analysis of the observational ARBALET study showed that indapamide/amlodipine SPC was associated with significant reductions in BP and high rates of target BP achievement in a broad age range of patients with ISH treated in routine clinical practice.
STUDY REGISTRATION NUMBER
ISRCTN40812831.
Topics: Aged; Amlodipine; Antihypertensive Agents; Blood Pressure; Drug Combinations; Female; Humans; Hypertension; Indapamide; Male; Middle Aged; Perindopril; Treatment Outcome
PubMed: 35246035
DOI: 10.1186/s12872-022-02514-y -
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 -
High Blood Pressure & Cardiovascular... May 2022Adequate controlled blood pressure decreases the risk of cardiovascular events. However, the elderly are more vulnerable and thereby more prone to side effects of...
DiffErenCes in AntihypertenSive Drug Blood Levels in Patients with HypertensiON (DECISION): Protocol for a Prospective Observational Study Comparing Pharmacokinetics and Pharmacodynamics Between Young and Elderly Patients.
Adequate controlled blood pressure decreases the risk of cardiovascular events. However, the elderly are more vulnerable and thereby more prone to side effects of antihypertensive drugs. A lack of pharmacokinetic and pharmacodynamic (PK/PD) studies in older patients makes specific and tailored advices towards antihypertensive drug therapy difficult. The aim of our study, DiffErenCes In antihypertenSive drug levels In patients with hypertensiON (DECISION), is to fill in this PK/PD knowledge gap and move towards precision dosing. DECISION is a prospective observational PK/PD study set up to determine the difference in exposure to the antihypertensive drugs, losartan and perindopril, measured by drug levels in blood. The area under the curve (AUC; PK) and furthermore the association between the AUC and the effect on blood pressure (PD) will be compared between elderly and younger patients.
Topics: Aged; Antihypertensive Agents; Blood Pressure; Humans; Hypertension; Observational Studies as Topic; Perindopril; Prospective Studies
PubMed: 35175576
DOI: 10.1007/s40292-022-00505-w -
Journal of Cachexia, Sarcopenia and... Apr 2022This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia.
METHODS
Placebo-controlled, parallel group, double-blind, randomized two-by-two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category-specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between-group difference in the short physical performance battery (SPPB) score over 12-month follow-up by repeated-measures mixed models. Results were combined with existing systematic reviews using random-effects meta-analysis to derive summary estimates of treatment efficacy.
RESULTS
We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect -0.1 points (95%CI -1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.4 kg (95%CI -1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI -1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect -0.3 kg (95%CI -1.0 to 0.4), P = 0.47]. Meta-analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between-group difference -0.1 points (95%CI -0.4 to 0.2)].
CONCLUSIONS
Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta-analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.
Topics: Aged; Female; Hand Strength; Humans; Leucine; Male; Meta-Analysis as Topic; Perindopril; Physical Functional Performance; Sarcopenia; Treatment Outcome
PubMed: 35174663
DOI: 10.1002/jcsm.12934 -
Synergistic actions between angiotensin-converting enzyme inhibitors and statins in atherosclerosis.Nutrition, Metabolism, and... Apr 2022Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and... (Review)
Review
AIMS
Hypertension and hypercholesterolemia are independent risk factors for atherosclerotic cardiovascular disease (ASCVD) by acting directly on the endothelium and activating the renin-angiotensin aldosterone system (RAAS) and mevalonate pathways. This review examines how the severity and duration of these risk factors may influence the cardiovascular risk through a reciprocal interplay leading to oxidative stress and pro-inflammatory response.
DATA SYNTHESIS
The review highlights the clinical evidence supporting the benefits of statins and angiotensin-converting enzyme (ACE) inhibitors for hypertension, lipid disorders and ASCVD management, both individually and combined, at all stages of the cardiovascular continuum.
CONCLUSION
Drug strategies incorporating an ACE-inhibitor and a statin, and in particular perindopril and atorvastatin, have consistently demonstrated reductions in the rate of ASCVD events in patients with hypertension and lipid disorders, cementing their position as first-line therapies for the management of atherosclerosis complications.
Topics: Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Atherosclerosis; Atorvastatin; Cardiovascular Diseases; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertension; Renin-Angiotensin System
PubMed: 35082055
DOI: 10.1016/j.numecd.2021.11.015