TY - JOUR
T1 - Protecting the myocardium
T2 - A role for the β2 adrenergic receptor in the heart
AU - Patterson, Andrew J.
AU - Zhu, Weizhong
AU - Chow, Amy
AU - Agrawal, Rani
AU - Kosek, Jon
AU - Xiao, Rui Ping
AU - Kobilka, Brian
PY - 2004/4
Y1 - 2004/4
N2 - 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.
AB - 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.
KW - Adrenoceptor
KW - Apoptosis
KW - Heart failure
KW - Knockout
KW - Myocardium
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U2 - 10.1097/01.CCM.0000120049.43113.90
DO - 10.1097/01.CCM.0000120049.43113.90
M3 - Article
C2 - 15071399
AN - SCOPUS:1842788823
SN - 0090-3493
VL - 32
SP - 1041
EP - 1048
JO - Critical care medicine
JF - Critical care medicine
IS - 4
ER -