title: Endothelial dysfunction in rat mesenteric resistance artery after transient middle cerebral artery occlusion.
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-1beta 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 (O(2)(.)) production was evaluated by ethidium fluorescence. In MRA, ischemia/reperfusion increased plasma levels of IL-6, O2. 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, N(omega)-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 O2. in MRA mediates endothelial dysfunction, and the increase in plasma cytokine levels after brain ischemia/reperfusion might be involved in this effect.
authors.affiliation: Departament de Farmacologia, Terapèutica i Toxicologia, Institut de Neurociències, Facultat de Medicina, Universitat Autònoma de Barcelona, 08193 Bellaterra, Spain.
authors.forename: Sonia
authors.initials: S
authors.lastname: Martinez-Revelles
authors.forename: Francesc
authors.initials: F
authors.lastname: Jiménez-Altayó
authors.forename: Laura
authors.initials: L
authors.lastname: Caracuel
authors.forename: Fernando J
authors.initials: FJ
authors.lastname: Pérez-Asensio
authors.forename: Anna M
authors.initials: AM
authors.lastname: Planas
authors.forename: Elisabet
authors.initials: E
authors.lastname: Vila
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D007213:Indomethacin / Q000494:pharmacology; D020244:Infarction, Middle Cerebral Artery / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D053583:Interleukin-1beta / Q000097:blood*; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D016861:Cyclooxygenase Inhibitors; D053583:Interleukin-1beta; D015850:Interleukin-6; D014665:Vasodilator Agents; D013481:Superoxides; D009599:Nitroprusside; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; D013482:Superoxide Dismutase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin