Adenosine A(2A)R modulates cardiovascular function by activating ERK1/2 signal in the rostral ventrolateral medulla of acute myocardial ischemic rats

Abstract

Aims: To investigate the cardiovascular regulatory mechanism of adenosine A(2A) receptor (A(2A)R) in the rostral ventrolateral medulla (RVLM) in acute myocardial ischemic (AMI) rats.

Main methods: The animal model of AMI was established by ligating the left anterior descending coronary artery (LAD). The A(2A)R expression was examined by immunohistochemistry, western blot and real-time PCR. CGS21680 and SCH58261 (an agonist and antagonist of A(2A)R) were respectively microinjected into the RVLM. In a subgroup of rats, PD98059 (an antagonist of extracellular signal-regulated kinase (ERK1/2)) was microinjected prior to CGS21680 administration. Phosphorylation of ERK1/2 was examined by western blot.

Key findings: Our results demonstrated that A(2A)R immunoreactive positive neurons, the expressions of protein and mRNA of A(2A)R in the RVLM of AMI group were increased compared with the sham group. Microinjection CGS21680 into the RVLM inhibited mean arterial pressure (MAP) and heart rate (HR) in both AMI and sham groups. The inhibition was significantly greater in AMI group than in sham group. The cardiovascular effects of CGS21680 mentioned above were almost abolished by prior administration of PD98059. The increase of ERK1/2 in the RVLM with the cardiovascular responses was induced by CGS21680 in AMI rats; this effect was also blocked by SCH58261.

Significance: This study reveals that the activated A(2A)R in the RVLM underlies the depressor and bradycardiac responses in AMI rats via phosphorylation of ERK1/2 increasing.