Protecting the myocardium: A role for the β2 adrenergic receptor in the heart

Andrew J. Patterson, Weizhong Zhu, Amy Chow, Rani Agrawal, Jon Kosek, Rui Ping Xiao, Brian Kobilka

Research output: Contribution to journalArticlepeer-review

81 Scopus citations

Abstract

Objective: The sympathetic nervous system enhances cardiac muscle function by activating β adrenergic receptors (βARs). Recent studies suggest that chronic βAR stimulation is detrimental, however, and that it may play a role in the clinical deterioration of patients with congestive heart failure. To examine the impact of chronic β1AR and β2AR subtype stimulation individually, we studied the cardiovascular effects of catecholamine infusions in βAR subtype knockout mice (β1K0, β2K0). Design: Prospective, randomized, experimental study. Setting: Animal research laboratory. Subjects: β1K0 and β2K0 mice and wild-type controls. Interventions: The animals were subjected to 2 wks of continuous Infusion of the βAR agonist isoproterenol. Analyses of cardiac function and structure were performed during and 3 days after completion of the infusions. Functional studies included graded exercise treadmill testing, in vivo assessments of left ventricular function using Mikro-Tip catheter transducers, right ventricular pressure measurements, and analyses of organ weight to body weight ratios. Structural studies included heart weight measurements, assessments of myocyte ultrastructure using electron microscopy, and in situ terminal deoxynucleotidyl transferase-mediated biotin-dUTP nick-end labeling staining to quantitate myocyte apoptosis. Measurements and Main Results: We found that isoproterenol-treated β2K0 mice experienced greater mortality rates (p = .001, chi-square test using Fisher's exact method) and increased myocyte apoptosis at 3- and 7-day time points (p = .04 and p = .0007, respectively, two-way analysis of variance). Conclusion: The results of this study suggest that in vivo β2AR activation is antiapoptotic and contributes to myocardial protection.

Original languageEnglish (US)
Pages (from-to)1041-1048
Number of pages8
JournalCritical care medicine
Volume32
Issue number4
DOIs
StatePublished - Apr 2004

Keywords

  • Adrenoceptor
  • Apoptosis
  • Heart failure
  • Knockout
  • Myocardium

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

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