Cerebral Ischemia Upregulates Vascular Endothelin ET B Receptors in Rat

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Abstract
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 (Emax [maximum contraction, calculated as percentage of the contractile capacity of 63.5 mmol/L K+]=68±68%; PA and ETB receptors (both PConclusions— 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.