Cardiac Alpha<sub>1</sub>-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

OʼConnell, Timothy D.; Jensen, Brian C.; Baker, Anthony J.; Simpson, Paul C.

doi:10.1124/pr.112.007203

Cited by 168 publications

(168 citation statements)

References 322 publications

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“…The α 1 AR subfamily (a G q -coupled receptor) consists of three highly homologous subtypes, including α 1 A-, α 1 B-, and α 1 D-AR [ 25 ]. The α 2 AR subfamily (coupled to G i ) comprises three subtypes: α 2 A-, α 2 B-, and α 2 C-AR [ 26 ]. Some species other than humans express a fourth α 2 D-AR as well [ 27 ].…”

Section: Adrenergic Signaling: Established Pathways and Novel Insightsmentioning

confidence: 99%

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Santulli

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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Heart failure represents the leading cause of death, especially among the elderly. Despite the development of numerous therapeutic strategies, heart failure prevalence is still increasing. Ergo, exploring the molecular mechanisms underlying aging-related heart failure seems to be of particular relevance. Intriguingly, the fi elds of cardiovascular disease and aging, which have remained largely separate hitherto, seem to have a common point in the sympathetic nervous system. Indeed, mounting evidence indicates that adrenergic receptors are functionally involved in numerous processes underlying both aging and cardiovascular disease. This chapter will review the pathophysiological role of the sympathetic nervous system in heart failure and cardiac aging.

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Section: Adrenergic Signaling: Established Pathways and Novel Insightsmentioning

confidence: 99%

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Santulli

2015

Pathophysiology and Pharmacotherapy of Cardiovascular Disease

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“…reported to increase inotropy and to promote hypertrophy, albeit these effects may be more prominent in rodents compared with humans O'Connell et al, 2014). a 1 -Adrenoceptor signaling induces the contraction of smooth muscle cells, thereby controlling blood pressure, bladder, and prostate tone and pupil width.…”

Section: Adrenoceptors As Drug Targetsmentioning

confidence: 99%

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

Ahles

Engelhardt

2014

Pharmacol Rev

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“…9,10 These effects may be particularly important in chronic HF, when catecholamine levels are elevated and β-ARs are downregulated and dysfunctional. 10 It is now generally accepted that, in the human heart, β1-and β2-ARs coexist; the existence of a third heart β-AR is to date mainly supported by the anomalous pattern of nonconventional partial agonists.…”

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confidence: 99%

The Autonomic Nervous System and Heart Failure

Florea

Cohn

2014

Circulation Research

419

346

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Abstract:The pathophysiology of heart failure (HF) is characterized by hemodynamic abnormalities that result in neurohormonal activation and autonomic imbalance with increase in sympathetic activity and withdrawal of vagal activity. Alterations in receptor activation from this autonomic imbalance may have profound effects on cardiac function and structure. Inhibition of the sympathetic drive to the heart through β-receptor blockade has become a standard component of therapy for HF with a dilated left ventricle because of its effectiveness in inhibiting the ventricular structural remodeling process and in prolonging life. Several devices for selective modulation of sympathetic and vagal activity have recently been developed in an attempt to alter the natural history of HF. The optimal counteraction of the excessive sympathetic activity is still unclear. A profound decrease in adrenergic support with excessive blockade of the sympathetic nervous system may result in adverse outcomes in clinical HF. In this review, we analyze the data supporting a contributory role of the autonomic functional alterations on the course of HF, the techniques used to assess autonomic nervous system activity, the evidence for clinical effectiveness of pharmacological and device interventions, and the potential future role of autonomic nervous system modifiers in the management of this syndrome. (Circ Res. 2014;114:1815-1826.) Key Words: autonomic nervous system ■ heart failure ■ norepinephrine ■ receptors, adrenergicThe Autonomic Nervous System and Heart Failure Viorel G. Florea, Jay N. Cohn This Review is in a thematic series on The Autonomic Nervous System and the Cardiovascular System, which includes the following articles: Role of the Autonomic Nervous System in Modulating Cardiac Arrhythmias [Circ Res. 2014;114:1004-1021 The Autonomic Nervous System and Hypertension [Circ Res. 2014;114:1804-1814 The Autonomic Nervous System and Heart Failure Renal Denervation for the Treatment of Cardiovascular High Risk-Hypertension or Beyond? Original received February 10, 2014; revision received April 29, 2014; accepted April 29, 2014. In March 2014, the average time from submission to first decision for all original research papers submitted to Circulation Research was 12.63 days.From the Minneapolis VA Health Care System, Section of Cardiology (V.G.F.) and Rasmussen Center for Cardiovascular Disease Prevention, Department of Medicine (J.N.C.), University of Minnesota Medical School.Correspondence to Jay N. endocardium. Parasympathetic effects are carried by the right and left vagus nerves, originating in the medulla. The vagus nerve further divides into the superior and inferior cardiac nerves, finally merging with the postganglionic sympathetic neurons to form a plexus of nerves at the base of the heart, known as the cardiac plexus. 1The 2 mediators of the SNS, norepinephrine and epinephrine, derive from 2 major sources in the body: the sympathetic nerve endings, which release norepinephrine directly into the synaptic cleft, and the adren...

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Cardiac Alpha₁-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

Cited by 168 publications

References 322 publications

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

The Autonomic Nervous System and Heart Failure

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Cardiac Alpha1-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance

Cited by 168 publications

References 322 publications

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Sympathetic Nervous System Signaling in Heart Failure and Cardiac Aging

Polymorphic Variants of Adrenoceptors: Pharmacology, Physiology, and Role in Disease

The Autonomic Nervous System and Heart Failure

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Product

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Cardiac Alpha₁-Adrenergic Receptors: Novel Aspects of Expression, Signaling Mechanisms, Physiologic Function, and Clinical Importance