Cerebral ischemia upregulates vascular endothelin ET(B) receptors in rat.
OBJECTIVE
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 ET(A) and ET(B) receptor agonist, and sarafotoxin 6c (S6c), a selective ET(B) 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(max) [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 ET(A) and ET(B) 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 ET(A) and ET(B) receptors, which results in the appearance of a contractile response to the ET(B) receptor agonist S6c. These results suggest a role for ET receptors in the pathogenesis of a vascular component after cerebral ischemia.
Stenman
Emelie
E
Division of Experimental Vascular Research, Department of Internal Medicine, Lund University Hospital, Lund, Sweden. Emelie.Stenman@med.lu.se
Malmsjö
Malin
M
Uddman
Erik
E
Gidö
Gunilla
G
Wieloch
Tadeuz
T
Edvinsson
Lars
L
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000503:physiopathology; D002545:Brain Ischemia / Q000209:etiology / Q000503:physiopathology*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000494:pharmacology; D066298:In Vitro Techniques; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D008297:Male; D020768:Middle Cerebral Artery / Q000187:drug effects / Q000503:physiopathology; D020648:Peptide Elongation Factor 1 / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014661:Vasoconstriction / Q000187:drug effects; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014757:Viper Venoms / Q000494:pharmacology
D019332:Endothelin-1; D020648:Peptide Elongation Factor 1; D012333:RNA, Messenger; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D017466:Receptors, Endothelin; D014662:Vasoconstrictor Agents; D014757:Viper Venoms; C057354:sarafotoxins s6