Male Wistar rats were subjected to 3 h middle cerebral artery occlusion (MCAO) and 21 h reperfusion. One group received ETA receptor antagonist atrasentan (5 mg/kg, i.p.) at reperfusion. At 24 h, basilar arteries were isolated from control non-stroked, stroked and stroked + atrasentan-treated animals for vascular reactivity measurements using pressurized arteriograph.
Acetylcholine (Ach)-induced maximum relaxation (Rmax) was decreased in stroked animals as compared to non-stroked group and ETA antagonism partially restored it. There was also a trend for decreased EC50 value for the antagonist treatment group indicating improved Ach sensitivity.
These findings suggest that I/R not only affects vessels distal to the occlusion but also impairs relaxation of proximal large vessels. ET-1-mediated basilar artery dysfunction may contribute to neurovascular damage after stroke and early restoration of vascular function by ET receptor antagonism after I/R injury may offer a therapeutic strategy.