Abstract 15416: Evidence for the Involvement of NADPH Oxidase in Adenosine Receptors-Mediated Control of Coronary Flow Using Knockout Mice
The NADPH oxidase (Nox) is the major source for reactive oxygen species (ROS) in cardiovascular system. In conditions such as ischemia-reperfusion injury and hypoxia, both ROS and adenosine are released suggesting a possible interaction. A2A and A2B adenosine receptors (ARs) are involved in coronary vasodilation, while A1AR and A3AR have been shown to decrease coronary flow (CF). Our aim in this study is to examine the role of A1AR and A3AR in control of CF and their relationship with Nox using isolated hearts from wild type (WT; C57/BL6) and A1 and A3 AR double knockout (A1/A3DKO) mice. The basal CF was significantly (p<0.05, n=12) higher in A1/A3DKO (20.9±1.6 ml/min/g tissue) compared to WT (16.7±1.6 ml/min/g tissue), suggesting negative roles for A1AR and A3AR in the control of CF. Moreover, adenosine concentration-response curve (10-8-10-5.5 M) produced increasing CF with Emax in A1/A3DKO (42.75±0.53 ml/min/g tissue) significantly (p<0.05, n=8) higher compared to WT (38.28±0.38 ml/min/g tissue). Inhibition of Nox by apocynin (10-5 M) significantly (p<0.001, n=6) decreased the enhanced CF to adenosine in both WT (Emax= 33.97±0.51 ml/min/g tissue) and A1/A3DKO (Emax= 31.86±1.07 ml/min/g tissue). The CF in A1/A3DKO was more sensitive (25.47 % decrease) to apocynin inhibition compared to WT (11.26% decrease), suggesting that Nox is involved mainly in adenosine-induced coronary vasodilation more than constriction. In conclusion, both A1AR and A3AR play a negative role in the control of CF, with Nox being involved as a major signaling pathway in adenosine-induced coronary vasodilation. The specific involvement of either A1AR or A3AR and the role of A2AAR, A2BAR and different Nox isoforms are being investigated.
- © 2011 by American Heart Association, Inc.