ArticleAmerican journal of physiology. Heart and circulatory physiology2010
Heart failure switches the RV alpha1-adrenergic inotropic response from negative to positive.
Article in American journal of physiology. Heart and circulatory physiology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis that pooled it.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.
- Cardiac and Vascular αCells · 2020Pooled it
- Ventricle-Specific Biomechanical Responses to Inotropic and Vasoactive Drugs in Human Myocardial Slices.Journal of cardiovascular translational research · 2026Article
- Mechanisms for the α-Adrenoceptor-Mediated Positive Inotropy in Mouse Ventricular Myocardium: Enhancing Effect of Action Potential Prolongation.International journal of molecular sciences · 2023Article
- Computational models of ventricular mechanics and adaptation in response to right-ventricular pressure overload.Frontiers in physiology · 2022Review
- 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
- Cardiac α1A-adrenergic receptors: emerging protective roles in cardiovascular diseases.American journal of physiology. Heart and circulatory physiology · 2021Review
- Human Myocardium Has a Robust α1A-Subtype Adrenergic Receptor Inotropic Response.Journal of cardiovascular pharmacology · 2018Article
- Multiscale Computational Analysis of Right Ventricular Mechanoenergetics.Journal of biomechanical engineering · 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
- Adrenergic Receptors in Individual Ventricular Myocytes: The Beta-1 and Alpha-1B Are in All Cells, the Alpha-1A Is in a Subpopulation, and the Beta-2 and Beta-3 Are Mostly Absent.Circulation research · 2017Article
- Emergency Spatiotemporal Shift: The Response of Protein Kinase D to Stress Signals in the Cardiovascular System.Frontiers in pharmacology · 2017Review
- Molecular Mechanisms of Right Ventricular Failure.Circulation · 2015Review
- The α1A-adrenergic receptor subtype mediates increased contraction of failing right ventricular myocardium.American journal of physiology. Heart and circulatory physiology · 2015Article
- Right ventricular adaptation and failure in pulmonary arterial hypertension.The Canadian journal of cardiology · 2015Review
- Adrenergic signaling in heart failure: a balance of toxic and protective effects.Pflugers Archiv : European journal of physiology · 2014Review
- Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation.Journal of cardiovascular pharmacology · 2014Review
- Cardiac alpha1-adrenergic receptors: novel aspects of expression, signaling mechanisms, physiologic function, and clinical importance.Pharmacological reviews · 2014Review
- Altered ubiquitin-proteasome signaling in right ventricular hypertrophy and failure.American journal of physiology. Heart and circulatory physiology · 2013Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Right ventricular (RV) failure is a serious common clinical problem that is poorly understood. Therefore, for failing and nonfailing hearts, we examined the distinctive inotropic responses induced in the RV myocardium after the stimulation of alpha(1)-adrenergic receptors (ARs). In RV trabeculae from nonfailing mouse hearts, alpha(1)-ARs induced a negative inotropic response, consistent with our previous study. In marked contrast, in RV trabeculae from failing hearts, 12 wk after coronary artery ligation, alpha(1)-ARs induced a positive inotropic response. Mechanistically, experiments with skinned trabeculae showed that alpha(1)-ARs decreased myofilament Ca(2+) sensitivity in the nonfailing RV myocardium, whereas alpha(1)-ARs increased Ca(2+) sensitivity in heart failure. This suggests that a switch in the Ca(2+) sensitivity response to alpha(1)-AR stimulation explained the switch in the RV alpha(1)-AR inotropic response in heart failure. Myosin light chain kinase (MLCK) can increase myofilament Ca(2+) sensitivity, and the smooth muscle isoform (smMLCK), which is also present in cardiomyocytes, was more abundant in the RV myocardium from failing versus nonfailing hearts. Moreover, the MLCK inhibitor ML-9 prevented the switch of the RV myocardium to a positive alpha(1)-AR inotropic response in heart failure. In the left ventricular myocardium, in contrast, alpha(1)-AR inotropic responses were not different in failing versus nonfailing hearts, and smMLCK abundance was not increased in heart failure. In relation to human disease, we found that smMLCK mRNA and protein levels were increased in RVs from failing human hearts. We conclude that the RV inotropic response to alpha(1)-ARs is switched from negative to positive in heart failure, through a pathway involving increased myofilament Ca(2+) sensitivity. Since alpha(1)-AR agonist catecholamines are elevated in heart failure, increased alpha(1)-AR inotropic responses in the RV myocardium may be adaptive in heart failure by helping the failing RV respond to increased pulmonary pressures.
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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.