title: Larger anastomoses in angiotensinogen-knockout mice attenuate early metabolic disturbances after middle cerebral artery occlusion.
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.
authors.affiliation: Max-Planck-Institute for Neurological Research, Department of Experimental Neurology, Cologne, Germany.
authors.forename: K
authors.initials: K
authors.lastname: Maeda
authors.forename: R
authors.initials: R
authors.lastname: Hata
authors.forename: M
authors.initials: M
authors.lastname: Bader
authors.forename: T
authors.initials: T
authors.lastname: Walther
authors.forename: K A
authors.initials: KA
authors.lastname: Hossmann
mesh_terms: D000208:Acute Disease; D000255:Adenosine Triphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000235:genetics*; D000818:Animals; D020771:Anterior Cerebral Artery / Q000473:pathology; D001157:Arterial Occlusive Diseases / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002545:Brain Ischemia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002560:Cerebrovascular Circulation / Q000235:genetics; D003097:Collateral Circulation / Q000502:physiology*; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D007840:Latex; D051379:Mice; D018345:Mice, Knockout; D020768:Middle Cerebral Artery / Q000473:pathology; D012084:Renin-Angiotensin System / Q000235:genetics; D020521:Stroke / Q000628:therapy
chemical_list: D007840:Latex; D000804:Angiotensin II; D000255:Adenosine Triphosphate