Abstract
Cerebral ischemia followed by reperfusion alters vessel properties of brain arteries in rats, inducing an inflammatory response and excessive generation of reactive oxygen species. This study investigated the participation of oxidative stress on vessel properties after ischemia/reperfusion and the beneficial effects of 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6). The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Ischemic rats were treated either with CR-6 (100 mg/kg in 1 ml olive oil) or vehicle (1 ml olive oil) administered orally at 2 and 8 h after the onset of ischemia. The structural, mechanical, and myogenic properties of the middle cerebral artery (MCA) were assessed by pressure myography. Superoxide anion () production was evaluated by ethidium fluorescence, and protein tyrosine nitrosylation was determined by immunofluorescence. Infarct volume was smaller in rats treated with CR-6. In MCA, ischemia/reperfusion increased wall thickness, cross-sectional area, wall/lumen, and decreased wall stress. CR-6 treatment prevented all of these changes induced by ischemia/reperfusion. However, impaired myogenic response and larger lumen diameter in active conditions observed after ischemia/reperfusion were not modified by CR-6. Treatment with CR-6 prevented the increase in production and partially prevented the enhanced protein tyrosine nitrosylation that occurred in response to ischemia/reperfusion. Our findings suggest that oxidative stress is involved in the alterations of MCA properties observed after ischemia/reperfusion and that CR-6 induces protection.
- ROS, reactive oxygen species
- MCA, middle cerebral artery
- I/R, ischemia/reperfusion
- CR-6, 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran
- KHS, Krebs-Henseleit solution
- DHE, dihydroethidium
- SOD, superoxide dismutase
- ANOVA, analysis of variance
- CSA, cross-sectional area
- PEG, polyethylene glycol
- WT, wall thickness
- DiCa2+, internal diameter measured in active condition (2.5 mM Ca2+-Krebs-Henseleit solution)
- Di0Ca2+, internal diameter measured in passive condition (0 Ca2+-Krebs-Henseleit solution).
Footnotes
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This work was supported by the Dirección General de Investigación Científica y Tecnológica [Grants SAF2007-60406, SAF2008-04515, SAF2008-00048]. L.C. was supported by Universitat Autònoma de Barcelona [Formacio Investigadors]. S.M.-R. was supported by Ministerio de Educación y Ciencia [Formación de Profesorado Universitario]. F.J.P.-A. was supported by Ministerio de Educación y Ciencia [Juan de la Cierva Program].
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Part of this work was presented previously: Jiménez-Altayó F, Pérez-Asensio FJ, Caracuel L, Messeguer A, Planas AM, and Vila E (2007) Antioxidant treatment prevents middle cerebral artery (mca) structural alterations after transient focal ischemia in rats. British Pharmacological Society Winter Meeting; 2007 Dec 18–20; Brighton, UK.
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
doi:10.1124/jpet.109.157131
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ABBREVIATIONS:
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F.J.-A. and L.C. contributed equally to this work.
- Received June 8, 2009.
- Accepted August 18, 2009.
- © 2009 by The American Society for Pharmacology and Experimental Therapeutics
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