ArticleAmerican journal of physiology. Heart and circulatory physiology2015
The α1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium.
Article in American journal of physiology. Heart and circulatory physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Cardiac and Vascular αCells · 2020Pooled it
- Role of α-adrenergic activation during the hemodynamic response to maternal hyperoxygenation in fetal sheep†.Biology of reproduction · 2026Article
- Chronic therapy with α1A-adrenergic agonist reverses RV failure and mitochondrial dysfunction.bioRxiv : the preprint server for biology · 2026Article
- Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.Nature communications · 2024Article
- The selective serotonin reuptake inhibitor paroxetine improves right ventricular systolic function in experimental pulmonary hypertension.Journal of molecular and cellular cardiology plus · 2024Article
- αInternational journal of molecular sciences · 2023Review
- Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation.International journal of molecular sciences · 2023Article
- α1-Adrenergic receptor regulates papillary muscle and aortic segment contractile function via modulation of store-operated CaJournal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2021Article
- Targeting Adrenergic Receptors in Metabolic Therapies for Heart Failure.International journal of molecular sciences · 2021Review
- Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2021Review
- Current Developments on the Role of αFrontiers in cell and developmental biology · 2021Review
- Emerging therapies for right ventricular dysfunction and failure.Cardiovascular diagnosis and therapy · 2020Review
- Coupling to Gq Signaling Is Required for Cardioprotection by an Alpha-1A-Adrenergic Receptor Agonist.Circulation research · 2019Article
- Calcium/calmodulin regulates signaling at the αEuropean journal of pharmacology · 2019Article
- Monitoring the Health Status of Mice with Bleomycin-induced Lung Injury by Using Body Condition Scoring.Comparative medicine · 2019Article
- Human Myocardium Has a Robust α1A-Subtype Adrenergic Receptor Inotropic Response.Journal of cardiovascular pharmacology · 2018Article
- The Role of G Protein-Coupled Receptors in the Right Ventricle in Pulmonary Hypertension.Frontiers in cardiovascular medicine · 2018Review
- Impaired Myofilament Contraction Drives Right Ventricular Failure Secondary to Pressure Overload: Model Simulations, Experimental Validation, and Treatment Predictions.Frontiers in physiology · 2018Article
- αAmerican journal of physiology. Heart and circulatory physiology · 2017Article
- An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity.JACC. Basic to translational science · 2017Article
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Dysfunction of the right ventricle (RV) is closely related to prognosis for patients with RV failure. Therefore, strategies to improve failing RV function are significant. In a mouse RV failure model, we previously reported that α1-adrenergic receptor (α1-AR) inotropic responses are increased. The present study determined the roles of both predominant cardiac α1-AR subtypes (α1A and α1B) in upregulated inotropy in failing RV. We used the mouse model of bleomycin-induced pulmonary fibrosis, pulmonary hypertension, and RV failure. We assessed the myocardial contractile response in vitro to stimulation of the α1A-subtype (using α1A-subtype-selective agonist A61603) and α1B-subtype [using α1A-subtype knockout mice and nonsubtype selective α1-AR agonist phenylephrine (PE)]. In wild-type nonfailing RV, a negative inotropic effect of α1-AR stimulation with PE (force decreased ≈50%) was switched to a positive inotropic effect (PIE) with bleomycin-induced RV injury. Upregulated inotropy in failing RV occurred with α1A-subtype stimulation (force increased ≈200%), but not with α1B-subtype stimulation (force decreased ≈50%). Upregulated inotropy mediated by the α1A-subtype involved increased activator Ca(2+) transients and increased phosphorylation of myosin regulatory light chain (a mediator of increased myofilament Ca(2+) sensitivity). In failing RV, the PIE elicited by the α1A-subtype was appreciably less when the α1A-subtype was stimulated in combination with the α1B-subtype, suggesting functional antagonism between α1A- and α1B-subtypes. In conclusion, upregulation of α1-AR inotropy in failing RV myocardium requires the α1A-subtype and is opposed by the α1B-subtype. The α1A subtype might be a therapeutic target to improve the function of the failing RV.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.