Effect of Angiotensin II Type 2 Receptor Deletion in Hematopoietic Cells on Brain Ischemia-Reperfusion Injury
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 AT2 receptor in ischemic brain damage. Here, we investigated the effect of AT2 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 AT2 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 AT2 receptor in blood cells has a harmful effect on ischemic brain injury.
- Received June 10, 2011.
- Revision received June 18, 2011.
- Accepted June 23, 2011.
- © 2011 American Heart Association, Inc.