Role of adenosine A2A receptor in organ-specific vascular reactivity following hemorrhagic shock in rats

Abstract Background Previous studies have demonstrated differences among organs in terms of shock-induced vascular reactivity and a role for adenosine A2A receptors (A2ARs) in protection against ischemia/reperfusion injury. However, the contributions of A2ARs to organ-specific vascular reactivity and the protection of vascular responsiveness following shock are currently unknown. Methods We investigated the role of A2ARs in different arteries, including the left femoral artery (LFA), thoracic aorta (TA), superior mesenteric artery (SMA), right renal artery (RRA), pulmonary artery (PA), and middle cerebral artery (MCA), in hemorrhagic-shock rats. Results The vascular reactivities of the LFA, SMA, RRA, and MCA increased slightly during early shock and then gradually decreased, whereas those of the PA and TA decreased from the start of shock. Different blood vessels lost vascular reactivity at different rates compared with controls; the LFA had the highest rate of loss (64.51%), followed by the SMA (44.69%), TA (36.06%), PA (37.83%), and RRA (32.33%), whereas the MCA had the lowest rate (18.45%). The rate of loss of vascular reactivity in the different vessels was negatively correlated with A2AR expression levels in normal and shock conditions. The highly selective A2AR agonist CGS 21680 significantly improved vascular reactivity, hemodynamic parameters, and animal survival, whereas the specific antagonist SCH58261 further decreased the shock-induced reduction in vascular reactivity and hemodynamic parameters. Conclusions A2ARs are involved in the regulation and protection of vascular reactivity following shock. A2AR activation may have a beneficial effect on hemorrhagic shock by improving vascular reactivity and hemodynamic parameters.