Abstract
It was shown previously that endothelin (ET) receptor antagonist (RO 61-1790) reversed the postischemic hypoperfusion and significantly increased the cerebral perfusion after transient ischemia and focal ischemia [4-h middle cerebral artery occlusion (MCAO)], respectively. The aim of the present study was to determine whether additional or repeated treatment with RO 61-1790 would reduce tissue injury in spontaneously hypertensive rats subjected to 24-h MCAO. RO 61-1790 (affinity for ETA receptor approximately 1000-fold higher than for ETB receptor) was a gift from Hoffmann-LaRoche Ltd. (Basel, Switzerland). Animals were injected twice with 10 mg/kg RO 61-1790 (5 min before MCAO and 5 h later) or 3 times with 10 mg/kg RO 61-1790 (5 min before MCAO) and 5 mg/kg RO 61-1790 (5 h and 8 h later). Animals injected with vehicle (saline) at identical time intervals served as controls. Ischemic lesion volume was assessed on the basis of 2% 2, 3, 5-triphenyltetrazolium-chloride monohydrate (TTC) staining using an image analyzer (NIH Image). There were no significant differences in cerebral infarct volume between the animals injected twice with RO 61-1790 and the respective controls (165.2 ± 22.2 mm3 vs. 174.8 ± 20.5 mm3, respectively). However, the infarct volumes in the animals injected 3 times with RO 61-1790 (147.5±18.9 mm3) were significantly decreased as compared to the controls (178.4±12.1 mm3). These findings indicate that treatment with the ETA antagonist, RO 61-1790, can ameliorate the cerebral infarct volume induced by MCAO. This effect is dependent upon the time and dose of RO 61-1790 treatment.
