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Antioxidant treatment prevents middle cerebral artery structural alterations after transient focal ischaemia in rats
Cerebral blood vessel properties could influence cerebral blood flow. The degree of blood flow reduction during brain ischemia and the extent of recovery at reperfusion determine the severity of brain damage (Coyle and Heistad, 1987). Cerebral ischemia followed by reperfusion alters vessel properties of brain arteries in rats (Cipolla et al., 1997; Jiménez-Altayó et al., 2007). CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran), is a nitric oxide and radical oxygen species s cavenger (Montoliu et al., 1999) that could be beneficial in brain ischemia. Therefore, we hypothesized that CR-6 treatment could influence the changes on vessel properties due to ischemia-reperfusion. Cerebral blood vessel properties could influence cerebral blood flow. The degree of blood flow reduction during brain ischemia and the extent of recovery at reperfusion determine the severity of brain damage (Coyle and Heistad, 1987). Cerebral ischemia followed by reperfusion alters vessel properties of brain arteries in rats (Cipolla et al., 1997; Jiménez-Altayó et al., 2007). CR-6 (3,4-dihydro-6-hydroxy-7-methoxy-2,2-dimethyl-1(2H)-benzopyran), is a nitric oxide and radical oxygen species scavenger (Montoliu et al., 1999) that could be beneficial in brain ischemia. Therefore, we hypothesized that CR-6 treatment could influence the changes on vessel properties due to ischemia-reperfusion. Male Sprague-Dawley rats (300-350 g) were subjected to transient middle cerebral artery (MCA) occlusion (90 min) followed by reperfusion (24 h). Rats were divided into 3 groups: sham-operated (n=6), vehicle (n=7) and CR-6 (n=7).Animals were treated at 30 min and 6.5 h reperfusion with CR-6 (100 mg/kg in 1 ml olive oil, p.o.) or vehicle (1 ml olive oil, p.o.). Afterwards, rats were killed under halothane anaesthesia and the MCA from the ipsilateral hemisphere was removed and placed in oxygenated physiological salt solution. The artery was set up in a pressure myograph under physiological conditions. Intraluminal pressure was increased stepwise from 3 to 120 mm Hg in the presence and in the absence of Ca2+. Lumen diameter, media, wall thickness and wall to lumen ratio were measured at increased pressures. Structural, mechanical and myogenic properties were calculated from these data. The results were statistically analysed by two way ANOVA with repeated measures in the pressure factor. Ischemia-reperfusion induced an increase in wall thickness (P<0.01), cross sectional area (P<0.05) and wall:lumen (P<0.01) that was prevented by CR-6. The wall stress but not the wall stiffness was significantly (P<0.01) decreased after ischemia–reperfusion. CR-6 reverted the observed wall stress change induced by ischemia-reperfusion.. The myogenic tone was decreased (P<0.001) and the lumen diameter in active conditions increased (P<0.05) by ischemia-reperfusion. None of the myogenic alterations were modified by CR-6 treatment. These results show that CR-6 treatment prevents MCA structural changes induced by ischemia-reperfusion suggesting a relationship between remodelling and free radical species. In addition, the finding that myogenic properties after ischemia-reperfusion are not modified by antioxidant treatment may suggest dissociation between myogenic tone impairment and structural changes, and that the former is not dependent on free radical formation.
This work was supported by FIS (04/1295; 04/1104). FP-A is supported by Juan de la Cierva Program (MEC). |
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