Protecting the myocardium: a role for the beta2 adrenergic receptor in the heart.
OBJECTIVE
The sympathetic nervous system enhances cardiac muscle function by activating beta adrenergic receptors (betaARs). Recent studies suggest that chronic betaAR 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 beta1AR and beta2AR subtype stimulation individually, we studied the cardiovascular effects of catecholamine infusions in betaAR subtype knockout mice (beta1KO, beta2KO).


METHODS
Prospective, randomized, experimental study.


METHODS
Animal research laboratory.


METHODS
beta1KO and beta2KO mice and wild-type controls.


METHODS
The animals were subjected to 2 wks of continuous infusion of the betaAR 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.


RESULTS
We found that isoproterenol-treated beta2KO 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).


CONCLUSIONS
The results of this study suggest that in vivo beta2AR activation is antiapoptotic and contributes to myocardial protection.
Patterson
Andrew J
AJ
Department of Anesthesia, Stanford University, Stanford, CA, USA. ajplanes@leland.stanford.edu
Zhu
Weizhong
W
Chow
Amy
A
Agrawal
Rani
R
Kosek
Jon
J
Xiao
Rui Ping
RP
Kobilka
Brian
B
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D005080:Exercise Test / Q000187:drug effects; D006321:Heart / Q000294:innervation; D007262:Infusions, Intravenous; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008854:Microscopy, Electron; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000473:pathology*; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects / Q000235:genetics; D018343:Receptors, Adrenergic, beta-2 / Q000187:drug effects* / Q000235:genetics; D015996:Survival Rate; D013564:Sympathetic Nervous System / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects*; D016278:Ventricular Function, Right / Q000187:drug effects*
D000318:Adrenergic beta-Agonists; D018342:Receptors, Adrenergic, beta-1; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol