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Alpha- 1 adrenergic receptor in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation
Nov 19, 2018
Authors: Jensen, Brian M.D., O’Connell, Timothy D., Ph.D., Simpson, Paul C. M.D.
Citation: Jensen, B. C., O’Connell, T. D., & Simpson, P. C. (2014). Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation. Journal of cardiovascular pharmacology, 63(4), 291-301.
Summary By: Cecil Guardado, ICEP Member
This article provides insight into the cardiovascular function of characterized G-protein coupled receptors known as alpha-1 adrenergic receptors and their response to catecholamine molecules. As stated by the authors, these receptors are distributed throughout ventricular and atrial heart regions of both humans and other mammalian organisms and may play vital roles in the development and progression of conditions such as chronic heart failure. According to Jensen, O’Connell and Simpson (2015), various studies have shown that α1-adrengergic receptors may contribute cardioprotective functions against heart failure through their three main subtype receptors α1A, α1B and α1D adrenergic receptors (AR). These receptors are found in different regions throughout heart muscle as α1A-ARs are normally found in epicardial coronary arteries of the myocardium, α1B-ARs are localized in epicardial coronary endothelial cells and α1D-ARs are distributed throughout coronary smooth muscle cells. Data from knockout mice experiments referenced in this article have suggested that both α1A and α1B-ARs may be involved in the regulation of cardiac stroke volume, blood pressure, normal heart growth and enlargement and coronary vasoconstriction and vasodilation. Moreover, it has been heavily implied that α1-ARs may actually support contractile function, preconditioned responses that oppose blood deficiency injuries to tissues and oppose pro-apoptotic processes that further amplify the deleterious progression of heart failure in response to chronic stimulation by catecholamines such as norepinephrine and epinephrine. Because α1-adrenergic receptors are G-protein coupled receptors bound to Gαq G-proteins, it has been suggested that they may exert their effects through signaling pathways that incorporate kinases such as protein kinase D and extracellular signal-regulated kinases 1/ 2 (ERKs 1 /2). Correspondingly, this article emphasizes the potential therapeutic benefits that alpha1-adrenergeic receptors may confer to patients with heart disease and especially the benefits they may impart in an effort to contrast β-adrenergic receptors’ disproportionate and suppressed function, which is unfortunately prevalent as part of chronic heart failure pathogenesis.
Keywords: GPCRs, Heart Failure, Adrenergic receptors, ERKs, Vascular Diseases, Coronary Arteries
Back to other Article Summaries
Alpha- 1 adrenergic receptor in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation
Nov 19, 2018
Authors: Jensen, Brian M.D., O’Connell, Timothy D., Ph.D., Simpson, Paul C. M.D.
Citation: Jensen, B. C., O’Connell, T. D., & Simpson, P. C. (2014). Alpha-1-adrenergic receptors in heart failure: the adaptive arm of the cardiac response to chronic catecholamine stimulation. Journal of cardiovascular pharmacology, 63(4), 291-301.
Summary By: Cecil Guardado, ICEP Member
This article provides insight into the cardiovascular function of characterized G-protein coupled receptors known as alpha-1 adrenergic receptors and their response to catecholamine molecules. As stated by the authors, these receptors are distributed throughout ventricular and atrial heart regions of both humans and other mammalian organisms and may play vital roles in the development and progression of conditions such as chronic heart failure. According to Jensen, O’Connell and Simpson (2015), various studies have shown that α1-adrengergic receptors may contribute cardioprotective functions against heart failure through their three main subtype receptors α1A, α1B and α1D adrenergic receptors (AR). These receptors are found in different regions throughout heart muscle as α1A-ARs are normally found in epicardial coronary arteries of the myocardium, α1B-ARs are localized in epicardial coronary endothelial cells and α1D-ARs are distributed throughout coronary smooth muscle cells. Data from knockout mice experiments referenced in this article have suggested that both α1A and α1B-ARs may be involved in the regulation of cardiac stroke volume, blood pressure, normal heart growth and enlargement and coronary vasoconstriction and vasodilation. Moreover, it has been heavily implied that α1-ARs may actually support contractile function, preconditioned responses that oppose blood deficiency injuries to tissues and oppose pro-apoptotic processes that further amplify the deleterious progression of heart failure in response to chronic stimulation by catecholamines such as norepinephrine and epinephrine. Because α1-adrenergic receptors are G-protein coupled receptors bound to Gαq G-proteins, it has been suggested that they may exert their effects through signaling pathways that incorporate kinases such as protein kinase D and extracellular signal-regulated kinases 1/ 2 (ERKs 1 /2). Correspondingly, this article emphasizes the potential therapeutic benefits that alpha1-adrenergeic receptors may confer to patients with heart disease and especially the benefits they may impart in an effort to contrast β-adrenergic receptors’ disproportionate and suppressed function, which is unfortunately prevalent as part of chronic heart failure pathogenesis.
Keywords: GPCRs, Heart Failure, Adrenergic receptors, ERKs, Vascular Diseases, Coronary Arteries
Back to other Article Summaries