PMCID: PMC2866766

NIHMSID: NIHMS182945

Beta 3-adrenoreceptor Regulation of Nitric Oxide in the Cardiovascular System

An L. Moens,^1,2,* Ronghua Yang,^1,* Vabren L. Watts,¹ and Lili A. Barouch¹

¹Johns Hopkins University School of Medicine, Div. of Cardiology, Baltimore, MD, US

²Cardiovascular Research Institute Maastricht, University of Maastricht, Maastricht, The Netherlands

Corresponding Author: Lili A. Barouch, MD, Johns Hopkins Medical Institutions, Div. of Cardiology, Ross Research Building 1050, 720 Rutland Ave, Baltimore, MD, 21205, Email: Barouch@jhmi.edu , Tel: +1 (410) 502-0188, Fax: +1 (410) 614-0384

^*These authors contributed equally to this work

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from: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2866766/

 

Abstract

The presence of a third β-adrenergic receptor (β3-AR) in the cardiovascular system has challenged the classical paradigm of sympathetic regulation by β1- and β2-adrenergic receptors. While β3-AR’s role in the cardiovascular system remains controversial, increasing evidence suggests that it serves as a “brake” in sympathetic overstimulation - it is activated at high catecholamine concentrations, producing a negative inotropic effect that antagonizes β1-and β2-AR activity. The anti-adrenergic effects induced by β3-AR were initially linked to nitric oxide (NO) release via endothelial NO synthase (eNOS), although more recently it has been shown under some conditions to increase NO production in the cardiovascular system via the other two NOS isoforms, namely inducible NOS (iNOS) and neuronal NOS (nNOS). We summarize recent findings regarding β3-AR effects on the cardiovascular system and explore its prospective as a therapeutic target, particularly focusing on its emerging role as an important mediator of NO signaling in the pathogenesis of cardiovascular disorders.

Addendum:
 a bet blocker bystolic that stimulat beta3 and beta 3 agonist like myrbetric increase nitric oxide through beta 3 adrenergic receptors. Exercse also does the same:

PMCID: PMC3140870

NIHMSID: NIHMS298525

Exercise Protects Against Myocardial Ischemia-Reperfusion injury via stimulation of β₃-Adrenergic Receptors and Increased Nitric Oxide Signaling: Role of Nitrite and Nitrosothiols

John W. Calvert,¹ Marah Elston, Juan Pablo Aragón,¹ Chad K Nicholson,¹ Bridgette F Moody,¹ Rebecca L Hood,¹ Amy Sindler,² Susheel Gundewar,¹ Douglas R. Seals,² Lili A. Barouch,³ and David J. Lefer¹

¹ Department of Surgery, Division of Cardiothoracic Surgery, Carlyle Fraser Heart Center, Emory University School of Medicine, Atlanta, GA 30308

² Department of Integrative Physiology, University of Colorado at Boulder, Boulder, CO 80309, USA

³ Johns Hopkins University School of Medicine, Department of Medicine, Division of Cardiology, Baltimore, MD

Correspondence: David J. Lefer, Ph.D., Department of Surgery, Division of Cardiothoracic Surgery, Emory University School of Medicine, 550 Peachtree Street NE, Atlanta, GA 30308, Phone: 404-686-1820, Email: dlefer@emory.edu

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Abstract

Rationale

Exercise training confers sustainable protection against ischemia-reperfusion injury in animal models and has been associated with improved survival following a heart attack in humans. It is still unclear how exercise protects the heart, but it is apparent that endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) play a role.

Objective

To determine the role of β₃-adrenergic receptors (β₃-ARs), eNOS activation, and NO metabolites (nitrite and nitrosothiols) in the sustained cardioprotective effects of exercise

Methods and Results

Here we show that voluntary exercise reduces myocardial injury in mice following a 4-week training period and that these protective effects can be sustained for at least 1 week following the cessation of the training. The sustained cardioprotective effects of exercise are mediated by alterations in the phosphorylation status of eNOS (increase in serine 1177 and decrease in threonine 495) leading to an increase in NO generation and storage of NO metabolites (nitrite and nitrosothiols) in the heart. Further evidence revealed that the alterations in eNOS phosphorylation status and NO generation were mediated by β₃-AR stimulation and that in response to exercise a deficiency of β₃-ARs leads to an exacerbation of myocardial infarction following ischemia-reperfusion injury.

Conclusions

Our findings clearly demonstrate that exercise protects the heart against myocardial ischemia-reperfusion injury by stimulation of β₃-ARs and increased cardiac storage of nitric oxide metabolites (i.e., nitrite and nitrosothiols).