Abstract
Stroke triggers a local and systemic inflammatory response leading to the production of cytokines that can influence blood vessel reactivity. In this study, we aimed to assess whether cerebral ischemia/reperfusion could affect vasoconstriction and vasodilatation on mesenteric resistance arteries (MRA) from Wistar Kyoto rats. The right middle cerebral artery was occluded (90 min) and reperfused (24 h). Sham-operated animals were used as controls. Plasma levels of interleukin (IL)-6 and IL-1β were measured at 24 h. Vasoconstrictor and vasodilator responses were recorded in a wire myograph. Protein expression was determined by Western blot and immunofluorescence, and superoxide anion () production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, production, protein expression of cyclooxygenase-2, and protein tyrosine nitrosylation, but it impaired acetylcholine (ACh) vasodilatation without modifying the vasodilatations to sodium nitroprusside or the contractions to phenylephrine and KCl. Superoxide dismutase (SOD) and indomethacin reversed the impairment of ACh relaxation induced by ischemia/reperfusion. However, Nω-nitro-l-arginine methyl ester affected similarly ACh-induced vasodilatations in MRA of ischemic and sham-operated rats. Protein expression of endothelial and inducible nitric-oxide synthase, copper/zinc SOD, manganese SOD, and extracellular SOD was similar in both groups of rats. Our results show MRA endothelial dysfunction 24 h after brain ischemia/reperfusion. Excessive production of in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.
Footnotes
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This study was supported by Fondo de Investigaciones Sanitarias de la Seguridad Social Grants 04/1295 and 04/1104 and by Dirección General de Investigación Científica y Tecnológica Grants SAF2007-60406 and SAF2005-05793. S.M.-R. was supported by Ministerio de Educación y Ciencia (Formación de Profesorado Universitario). L.C. was supported by Universitat Autònoma de Barcelona (Formacio Investigadors), and F.J.P.-A. was supported by Juan de la Cierva Program (Ministerio de Educación y Ciencia).
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Article, publication date, and citation information can be found at http://jpet.aspetjournals.org.
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doi:10.1124/jpet.107.134619.
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ABBREVIATIONS: MRA, mesenteric resistance artery(ies); MCA, middle cerebral artery; IL, interleukin; KHS, Krebs-Henseleit solution; PBS, phosphate-buffered saline; ACh, acetylcholine; SNP, sodium nitroprusside; l-NAME, Nω-nitro-l-arginine methyl ester; COX, cyclooxygenase; SOD, superoxide dismutase; PEG, polyethylene glycol; eNOS, endothelial nitric-oxide synthase; iNOS, inducible nitric-oxide synthase; EC, extracellular; ANOVA, analysis of variance; ONOO–, peroxynitrite; ADV, adventitial layer; END, endothelial layer; MED, media layer; IEL, internal elastic lamina.
- Received November 22, 2007.
- Accepted February 6, 2008.
- The American Society for Pharmacology and Experimental Therapeutics
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