Larger Anastomoses in Angiotensinogen-Knockout Mice Attenuate Early Metabolic Disturbances after Middle Cerebral Artery Occlusion

Abnormalities in the homeostasis of the renin-angiotensin system have been implicated in the pathogenesis of vascular disorders, including stroke. The authors investigated whether angiotensinogen (AGN) knockout mice exhibit differences in brain susceptibility to focal ischemia, and whether such differences can be related to special features of the collateral circulation. Wild-type and AGN-knockout mice were submitted to permanent suture occlusion of the middle cerebral artery (MCA). The collateral vascular system was visualized by systemic latex infusion, and the ischemic lesions were identified by cresyl-violet staining. The core and penumbra of the evolving infarct were differentiated by bioluminescence and autoradiographic imaging of A TP and protein biosynthesis, respectively. In wild-type mice, mean arterial blood pressure was 95.0 ± 8.6 mm Hg, and the diameter of fully relaxed anastomotic vessels between the peripheral branches of the anterior and middle cerebral arteries 26.6 ± 4.0 μm In AGN knockouts, mean arterial blood pressure was significantly lower, 71.5 ± 8.5 mm Hg ( P