Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion

Item Type:	Article
Title:	Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion
Creators Name:	Maeda, K. and Hata, R. and Bader, M. and Walther, T. and Hossmann, K.A.
Abstract:	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 ATP 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 microm. In AGN knockouts, mean arterial blood pressure was significantly lower, 71.5 +/- 8.5 mm Hg (P < .01), and the anastomotic vessels were significantly larger, 29.4 +/- 4.6 microm (P < .01). One hour after MCA occlusion, AGN-knockout mice exhibited a smaller ischemic core (defined as the region of ATP depletion) but a larger penumbra (the area of disturbed protein synthesis with preserved ATP). At 24 hours after MCA occlusion, this difference disappeared, and histologically visible lesions were of similar size in both strains. The observations show that in AGN-knockout mice the more efficient collateral blood supply delays ischemic injury despite the lower blood pressure. Pharmacologic suppression of angiotensin formation may prolong the therapeutic window for treatment of infarcts.
Keywords:	Renin-Angiotensin System, Angiotensinogen, Angiotensin II, Anastomoses, ATP, Penumbra, Mutant Mice, Animals, Mice
Source:	Journal of Cerebral Blood Flow and Metabolism
ISSN:	0271-678X
Publisher:	Lippincott Williams & Wilkins
Volume:	19
Number:	10
Page Range:	1092-1098
Date:	October 1999
Official Publication:	https://doi.org/10.1097/00004647-199910000-00005
PubMed:	View item in PubMed

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