Effect of angiotensin II Type 2 receptor deletion in hematopoietic cells on brain ischemia-reperfusion injury

Abstract

The angiotensin II type 2 (AT2) receptor is expressed in bone marrow cells and may affect cell differentiation. We previously reported a beneficial role of the AT 2 receptor in ischemic brain damage. Here, we investigated the effect of AT 2 receptor stimulation in hematopoietic cells on ischemic brain injury using chimeric mice. Chimeric mice were generated by bone marrow transplantation into wild-type mice after irradiation. Bone marrow cells were prepared from wild-type (Agtr2 +) or AT 2 receptor-deficient mice (Agtr2 -). Six weeks after bone marrow transplantation, these chimeric mice were subjected to ischemia/reperfusion injury. Both Agtr2 + and Agtr2 - chimeric mice did not show a significant change in systolic and diastolic blood pressures, whereas body weight decreased in Agtr2 - chimera. Twenty-four hours after ischemia/reperfusion injury, ischemic brain damage in Agtr2 - chimera was exaggerated compared with that in Agtr2 + chimera. Moreover, cerebral blood flow in the peripheral region before and after ischemia/reperfusion injury was decreased in Agtr2 - chimera. The inflammatory response in the ipsilateral hemisphere was not significantly different, whereas tumor necrosis factor-α and monocyte chemoattractant protein 1 expressions tended to increase in the Agtr2 - chimeric brain. Expression of methylmethane sulfonate 2, which has a neuroprotective effect, was lower in the brain of Agtr2 - chimera. These results indicate that deletion of AT 2 receptor in blood cells has a harmful effect on ischemic brain injury. © 2011 American Heart Association, Inc.