Cerebral ischemia upregulates vascular endothelin ETB receptors in rat

Background and Purpose-Elevated levels of endothelin 1 (ET 1) have been reported in cerebral ischemia A role for ET may prove more important if the vascular receptors were changed We addressed whether there is any change in ET receptor expression in cerebral ischemia Methods-The right middle cerebral artery (MCA) was occluded in male Wistar rats for 2 hours with the intraluminal filament method The basilar artery and both MCAs were removed after 46 hours of recirculation The contractile responses to ET 1 a combined ETA and ETB receptor agonist and sarafotoxin 6c (S6c) a selective ETB receptor agonist were examined in vitro and ET receptor mRNA was quantified by real time polymerase chain reaction Results-S6c which had no contractile effect per se on fresh or sham operated rat cerebral arteries induced a marked contraction in the occluded MCA (E-m [maximum contraction calculated as percentage of the contractile capacity of 63 5 mmol/L K+] =68+/-68% P<0 0001) while there was no difference in the responses to ET 1 after cerebral ischemia Real time polymerase chain reaction revealed a significant upregulation of both the ETA and ETB receptors (both P<0 05) in the occluded MCA compared with the nonoccluded MCA from the same rats Conclusions-Focal cerebral ischemia in rat induces increased transcription of both ETA and ETB receptors which results in the appearance of a contractile response to the ETB receptor agonist S6c These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.