Participation of oxidative stress on rat middle cerebral artery changes induced by focal cerebral ischemia: beneficial effects of 3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran (CR-6).
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.
Jiménez-Altayó
Francesc
F
Departament de Farmacologia, Terapèutica i Toxicología, Facultat de Medicina, Universitat Autònoma de Barcelona, Barcelona, Spain.
Caracuel
Laura
L
Pérez-Asensio
Fernando J
FJ
Martínez-Revelles
Sonia
S
Messeguer
Angel
A
Planas
Anna M
AM
Vila
Elisabet
E
D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002545:Brain Ischemia / Q000473:pathology*; D005455:Fluorescent Antibody Technique; D016166:Free Radical Scavengers / Q000494:pharmacology; D008297:Male; D020768:Middle Cerebral Artery / Q000473:pathology*; D009213:Myography; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D026361:Reactive Nitrogen Species / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism; D014810:Vitamin E / Q000378:metabolism
D001578:Benzopyrans; C120400:CR 6; D016166:Free Radical Scavengers; D026361:Reactive Nitrogen Species; D017382:Reactive Oxygen Species; D014810:Vitamin E; D014443:Tyrosine