Activation of beta2-adrenergic receptor plays a pivotal role in generating the protective effect of ischemic preconditioning in rat hearts.
BACKGROUND
Ischemic preconditioning (IPC) protects hearts against ischemia by reducing infarct size. However, IPC does not preserve cardiac function, such as left ventricular peak developed pressure (LVPDP). Moreover, IPC fails to protect the post-myocardial infarct (MI) heart.


METHODS
Rat hearts were transfected with beta2-adrenergic receptor (B2AR) cDNA by the hemagglutinating virus of Japan-liposome method. After the gene transfer, the hearts were perfused in a Langendorff mode and preconditioned with two cycles of 5 min of ischemia and reperfusion. After 20 min of global ischemia, the hearts were reperfused under aerobic conditions for 90 min. LVPDP was measured as an indicator of the cardiac function.


RESULTS
LVPDP of ischemic hearts was well preserved by the combination treatment of IPC and gene transfer of B2AR, but not IPC or gene transfer of B2AR alone. Moreover, the treatment was beneficial to even the post-MI heart. On the contrary, gene transfer of beta-adrenergic receptor kinase 1 (BARK1) reduced the protective effect of IPC. We also found that the mRNA ratio of B2AR and BARK1 was well correlated with the preservation of the LVPDP.


CONCLUSIONS
The combination treatment of IPC and gene transfer of B2AR protects cardiac function against ischemia and it shows the beneficial effect also in post-MI hearts.
Mieno
Shigetoshi
S
Department of Thoracic and Cardiovascular Surgery, Osaka Medical College, Takatsuki, Japan. tho050@poh.osaka-med.ac.jp
Horimoto
Hitoshi
H
Sawa
Yoshiki
Y
Watanabe
Fusao
F
Furuya
Eisuke
E
Horimoto
Sachiko
S
Kishida
Kenji
K
Sasaki
Shinjiro
S
D000818:Animals; D003131:Combined Modality Therapy; D018076:DNA, Complementary; D054769:G-Protein-Coupled Receptor Kinase 2; D018014:Gene Transfer Techniques; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000502:physiology*; D016277:Ventricular Function, Left; D051552:beta-Adrenergic Receptor Kinases / Q000096:biosynthesis / Q000235:genetics
D018076:DNA, Complementary; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; C496569:Grk2 protein, rat; D051552:beta-Adrenergic Receptor Kinases; D054769:G-Protein-Coupled Receptor Kinase 2