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Experimental Physiology Aug 2021What is the central question of this study? We questioned whether an angiotensin-converting enzyme (ACE) inhibitor prevents skeletal muscle fibrosis in diabetic mice....
NEW FINDINGS
What is the central question of this study? We questioned whether an angiotensin-converting enzyme (ACE) inhibitor prevents skeletal muscle fibrosis in diabetic mice. What is the main finding and its importance? Administration of ACE inhibitor prevents the increase in skeletal muscle fibrosis during the early phase after induction of diabetes by streptozotocin. Our findings might provide a new therapeutic target for skeletal muscle abnormalities in diabetes.
ABSTRACT
Fibrosis is characterized by the excessive production and accumulation of extracellular matrix components, including collagen. Although the extracellular matrix is an essential component of skeletal muscle, fibrosis can have negative effects on muscle function. Skeletal muscle fibrosis was shown to be increased in spontaneously hypertensive rats and to be prevented by an angiotensin-converting enzyme (ACE) inhibitor, an antihypertensive drug, in dystrophic mice or a mouse model of myocardial infarction. In this study, we therefore analysed whether (1) there is increased skeletal muscle fibrosis in streptozotocin (STZ)-induced diabetic mice, and (2) a preventive effect on skeletal muscle fibrosis by administration of an ACE inhibitor. Skeletal muscle fibrosis was significantly increased in STZ-induced diabetic mice compared with control mice from 2 to 14 days post-STZ. The ACE inhibitor prevented both skeletal muscle fibrosis and the reduction in muscle function in STZ-treated mice. Our study demonstrated that administration of an ACE inhibitor prevents the increase in skeletal muscle fibrosis during the early phase after onset of diabetes. Our findings might provide a new therapeutic target for skeletal muscle abnormalities in diabetes. Future studies are required to clarify whether skeletal muscle fibrosis is also linked directly to physical activity.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Diabetes Mellitus, Experimental; Fibrosis; Mice; Muscle, Skeletal; Rats
PubMed: 33998079
DOI: 10.1113/EP089375 -
Vascular Health and Risk Management Sep 2010Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in... (Review)
Review
Combination therapy is necessary for most patients with hypertension, and agents that inhibit the renin-angiotensin-aldosterone system (RAAS) are mainstays in hypertension management, especially for patients at high cardiovascular and renal risk. Single blockade of the RAAS with an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) confers some cardiorenal protection; however, these agents do not extinguish the RAAS as evidenced by a reactive increase in plasma renin activity (PRA), a cardiovascular risk marker, and incomplete cardiorenal protection. Dual blockade with an ACE inhibitor and an ARB offers no additional benefit in patients with hypertension and normal renal and left ventricular function. Indeed, PRA increases synergistically with dual blockade. Aliskiren, the first direct renin inhibitor (DRI) to become available has provided an opportunity to study the merit of DRI/ARB combination treatment. By blocking the first and rate-limiting step in the RAAS, aliskiren reduces PRA by at least 70% and buffers the compensatory increase in PRA observed with ACE inhibitors and ARBs. The combination of a DRI and an ARB or an ACE inhibitor is an effective approach for lowering blood pressure; available data indicate that such combinations favorably affect proteinuria, left ventricular mass index, and brain natriuretic peptide in patients with albuminuria, left ventricular hypertrophy, and heart failure, respectively. Ongoing outcome studies will clarify the role of aliskiren and aliskiren-based combination RAAS blockade in patients with hypertension and those at high cardiorenal risk.
Topics: Amides; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Antihypertensive Agents; Blood Pressure; Drug Therapy, Combination; Fumarates; Humans; Hypertension; Renin-Angiotensin System; Tetrazoles; Valine; Valsartan
PubMed: 20859542
DOI: 10.2147/vhrm.s8175 -
Cardiovascular Drugs and Therapy Aug 2017Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug... (Review)
Review
Hypertension (HTN) is the most common chronic disease in the USA. Hypertensive patients frequently require repeat primary care visits to find an effective drug or drug combination to control their disease. Currently, patients are prescribed drugs for HTN based on race, age, and comorbidities and although the current guidelines are reasonable starting points for prescribing, 50% of hypertensive patients still fail to achieve target blood pressures. Despite numerous strategies to improve compliance, drug effectiveness, and optimization of initial drug choice, effectiveness has remained largely unchanged over the past two decades. Therefore, it is important to pursue alternative strategies to more effectively treat patients and to decrease medical costs. Additional precision medicine work is needed to identify factors associated with effectiveness of commonly used antihypertensive medications. The objective of this manuscript is to present a comprehensive review of the pharmacogenomic and metabolomic factors associated with ACEI and ARB effectiveness and safety.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Humans; Hypertension; Metabolomics; Pharmacogenetics; Practice Guidelines as Topic; Treatment Outcome
PubMed: 28741243
DOI: 10.1007/s10557-017-6733-2 -
The Journal of Frailty & Aging 2023There is conflicting evidence regarding the role of angiotensin-converting enzyme inhibitors and physical function. While some studies show improvements in muscle...
BACKGROUND
There is conflicting evidence regarding the role of angiotensin-converting enzyme inhibitors and physical function. While some studies show improvements in muscle strength and physical function, others show no significant difference or decreased performance. This ambiguity could be due to differential effects of angiotensin-converting enzyme inhibitor subtypes which can be categorized as centrally or peripherally-acting based upon their ability to cross the blood-brain barrier.
OBJECTIVE
The objective of this study is to compare physical performance measures among angiotensin-converting enzyme inhibitor subtype users.
METHODS
Design: Cross-sectional Setting: Ambulatory Participants: Performed in 364 participants in the Health and Retirement Study cohort who were ≥ 65 years (median age (IQR) 74.00 (69-80) years.
MEASUREMENTS
Average difference in hand grip (kg), gait speed(m/s) and peak expiratory flow (L/min).
RESULTS
Compared to participants on a peripherally-acting angiotensin-converting enzyme inhibitor (113 (31%)), those on a centrally-acting agent (251(69%)) had stronger grip strength 28.9 ±1.0 vs 26.3±1.0, p=.011 and higher peak expiratory flow rates 316.8±130.4 vs. 280.0±118.5, p= .011 in unadjusted analysis. After multiple adjustments the difference in PEF remained statistically significant (Estimate(CI) 26.5, 95% CI 2.24, 50.5, p = 0.032).
CONCLUSION
Our results suggest that in older adults the use of centrally-acting angiotensin-converting enzyme inhibitors compared to a peripherally acting angiotensin-converting enzyme inhibitors was associated with better lung function in older individuals.
Topics: Humans; Aged; Angiotensin-Converting Enzyme Inhibitors; Hand Strength; Cross-Sectional Studies; Muscle Strength; Physical Functional Performance
PubMed: 36946705
DOI: 10.14283/jfa.2023.10 -
Scientific Reports Mar 2022Heart failure is a multifactorial disease that affects an estimated 38 million people worldwide. Current pharmacotherapy of heart failure with reduced ejection fraction...
Heart failure is a multifactorial disease that affects an estimated 38 million people worldwide. Current pharmacotherapy of heart failure with reduced ejection fraction (HFrEF) includes combination therapy with angiotensin-converting enzyme inhibitors (ACEi) and β-adrenergic receptor blockers (β-AR blockers), a therapy also used as treatment for non-cardiac conditions. Our knowledge of the molecular changes accompanying treatment with ACEi and β-AR blockers is limited. Here, we applied proteomics and phosphoproteomics approaches to profile the global changes in protein abundance and phosphorylation state in cardiac left ventricles consequent to combination therapy of β-AR blocker and ACE inhibitor in HFrEF and control hearts. The phosphorylation changes induced by treatment were profoundly different for failing than for non-failing hearts. HFrEF was characterized by profound downregulation of mitochondrial proteins coupled with derangement of β-adrenergic and pyruvate dehydrogenase signaling. Upon treatment, phosphorylation changes consequent to HFrEF were reversed. In control hearts, treatment mainly led to downregulation of canonical PKA signaling. The observation of divergent signaling outcomes depending on disease state underscores the importance of evaluating drug effects within the context of the specific conditions present in the recipient heart.
Topics: Adrenergic beta-Antagonists; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Heart; Heart Failure; Humans; Stroke Volume
PubMed: 35306519
DOI: 10.1038/s41598-022-08534-0 -
Nature Reviews. Endocrinology Apr 2015The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure homeostasis and vascular injury and repair responses. The RAAS was originally thought to be an... (Review)
Review
The renin-angiotensin-aldosterone system (RAAS) regulates blood pressure homeostasis and vascular injury and repair responses. The RAAS was originally thought to be an endocrine system critically important in regulating blood pressure homeostasis. Yet, important local forms of the RAAS have been described in many tissues, which are mostly independent of the systemic RAAS. These systems have been associated with diverse physiological functions, but also with inflammation, fibrosis and target-organ damage. Pharmacological modulation of the RAAS has brought about important advances in preventing morbidity and mortality associated with cardiovascular disease. Yet, traditional RAAS blockers such as angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) only reduce the risk of disease progression in patients with established cardiovascular or renal disease by ∼20% compared with other therapies. As more components of the RAAS are described, other potential therapeutic targets emerge, which could provide improved cardiovascular and renal protection beyond that provided by an ACE inhibitor or ARB. This Review summarizes the present and future pharmacological manipulation of this important system.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Animals; Cardiovascular Diseases; Humans; Hypertension; Renin-Angiotensin System
PubMed: 25666495
DOI: 10.1038/nrendo.2015.6 -
Renal Failure Dec 2021
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; COVID-19; Humans; Renal Dialysis; SARS-CoV-2
PubMed: 34704916
DOI: 10.1080/0886022X.2021.1994419 -
International Journal of Molecular... Apr 2021Hypertension causes many deaths worldwide and has shown an increasing trend as a severe non-communicable disease. Conventional antihypertensive drugs inevitably cause... (Review)
Review
Hypertension causes many deaths worldwide and has shown an increasing trend as a severe non-communicable disease. Conventional antihypertensive drugs inevitably cause side effects, and great efforts have been made to exploit healthier and more-available substitutes. Microalgae have shown great potential in this regard and have been applied in the food and pharmaceutical industries. Some compounds in microalgae have been proven to have antihypertensive effects. Among these natural compounds, peptides from microalgae are promising angiotensin-converting enzyme (ACE) inhibitors because an increasing number of peptides show hypertensive effects and ACE inhibitory-like activity. In addition to acting as ACE inhibitors for the treatment of hypertension, these peptides have other probiotic properties, such as antioxidant and anti-inflammatory properties, that are important for the prevention and treatment of hypertension. Numerous studies have revealed the important bioactivities of ACE inhibitors and their mechanisms. This review discusses the antihypertensive effects, structure-activity relationships, molecular docking studies, interaction mechanisms, and other probiotic properties of microalgal ACE inhibitory peptides according to the current research related to microalgae as potential antihypertensive drugs. Possible research directions are proposed. This review contributes to a more comprehensive understanding of microalgal antihypertensive peptides.
Topics: Angiotensin-Converting Enzyme Inhibitors; Animals; Antihypertensive Agents; Binding Sites; Humans; Microalgae; Molecular Docking Simulation; Peptides
PubMed: 33920763
DOI: 10.3390/ijms22084068 -
PloS One 2012An insertion/deletion (I/D) variant in the angiotensin-converting enzyme (ACE) gene was associated with ACE inhibitor (ACEI)-related cough in previous studies. However,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
An insertion/deletion (I/D) variant in the angiotensin-converting enzyme (ACE) gene was associated with ACE inhibitor (ACEI)-related cough in previous studies. However, the results were inconsistent. Our objective was to assess the relationship between the ACE I/D polymorphism and ACEI-related cough by meta-analysis and to summarize all studies that are related to ACE I/D polymorphism and ACEI-cough and make a summary conclusion to provide reference for the researchers who attempt to conduct such a study.
METHODS
Databases including PubMed, EMbase, Cochrane Library, and China National Knowledge Infrastructure, were searched for genetic association studies. Data were extracted by two independent authors and pooled odds ratio (OR) with 95% confidence interval (CI) was calculated. Metaregression and subgroup analyses were performed to identify the source of heterogeneity.
RESULTS
Eleven trials, including 906 cases (ACEI-related cough) and 1,175 controls, were reviewed in the present meta-analysis. The random effects pooled OR was 1.16 (95%CI: 0.78-1.74, p=0.46) in the dominant model and 1.61 (95%CI: 1.18-2.20, p=0.003) in the recessive model. Heterogeneity was found among and within studies. Metaregression indicated that the effect size was positively associated with age and negatively associated with follow-up duration of ACEI treatment. Subgroup analysis revealed a significant association between ACE I/D polymorphism and ACEI-related cough in studies with mean age >60 y, but not in studies with mean age ≤ 60 y. No heterogeneity was found within each mean age subgroup. We also found no association between ACE I/D polymorphism and ACEI-related cough in studies with follow-up>2 mo or in studies in Caucasians. No heterogeneity was detected in these two subgroups.
CONCLUSIONS
Synthesis of the available evidence supports ACE I/D polymorphism as an age-dependent predictor for risk of ACEI-related cough.
Topics: Alleles; Angiotensin-Converting Enzyme Inhibitors; Case-Control Studies; Cough; Gene Deletion; Gene Frequency; Genotype; Humans; Mutagenesis, Insertional; Peptidyl-Dipeptidase A; Polymorphism, Genetic
PubMed: 22723835
DOI: 10.1371/journal.pone.0037396 -
Cardiovascular Drugs and Therapy May 1997ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to... (Review)
Review
ACE inhibitors have been shown to be effective in reducing the morbidity and mortality of patients with left ventricular systolic dysfunction, but their application to clinical practice in this situation is still limited. In part, the failure to prescribe an ACE inhibitor to a patient with left ventricular systolic dysfunction is due to perceptions regarding their side effects, such as cough and renal dysfunction. Relatively few patients with left ventricular systolic dysfunction and a serum creatinine > or = 2 mg/dl receive an ACE inhibitor in clinical practice. In this situation one should consider an agent such as fosinopril, which is metabolized by the liver as well as secreted by the kidney. In patients with moderate renal dysfunction, fosinopril has been well tolerated without an increase in serum creatinine. In patients who develop cough due to an ACE inhibitor, consideration should be given to an angiotensin II type 1 receptor blocking agent, such as losartan. The relative safety and efficacy of an ACE inhibitor compared with an angiotensin II type 1 receptor blocking agent is being explored in a prospective randomized trial (Evaluation of Losartan In The Elderly [ELITE]), as well as the safety and pharmacological effectiveness of adding an angiotensin II receptor antagonist to an ACE inhibitor (Randomized Angiotensin receptor antagonists-ACE-inhibitor Study [RAAS]). There may also be a role for the combination of an aldosterone receptor antagonists and an ACE inhibitor in patients with left ventricular systolic dysfunction. Once an ACE inhibitor is administered to a patient with left ventricular systolic dysfunction it should be continued indefinitely. ACE inhibitors may be of value not only in preventing the progression of heart failure but also in reversing endothelial dysfunction and preventing the development of atherosclerosis and its consequences, such as myocardial infarction.
Topics: Adrenergic beta-Antagonists; Aldosterone; Angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Bradykinin; Cardiac Output, Low; Cough; Creatinine; Drug Therapy, Combination; Humans; Randomized Controlled Trials as Topic; Ventricular Function, Left
PubMed: 9211022
DOI: 10.1023/a:1007795915009