Inhibition of protein kinase C signal reduces ET receptor expression and basilar vasospasm after subarachnoid hemorrhage in rats.
Endothelin-1 (ET-1), acting through specific ET(A) and/or ET(B) receptors, plays an important role in cerebral vasospasm after subarachnoid hemorrhage (SAH). However, the mechanism remains unclear. In the present study, ET receptors' expression in the basiliar artery during cerebral vasospasm and the possible involvement of protein kinase C (PKC) were investigated using immunofluorescence staining and reverse transcriptase polymerase chain reaction (RT-PCR) in a rat SAH model of delayed cerebral vasospasm (DCVS). The cross-sectional area of the basilar artery in the SAH model group decreased in 2-3 days, and then gradually returned to normal. ET(A) receptor expression in endothelial cells of the basilar artery increased in day 2 after SAH, peaked at day 3 and remained increased till day 14. ET(B) receptor expression increased significantly in endothelial cells at day 3, peaked at day 7 and remained until day 14. RT-PCR result also revealed increased expressions of similar trends, but the expression of ET(B) receptor mRNA level tended to increase earlier than the protein level. When PKC inhibitor (RO-31-7549, 10(-6) mol/L, 50 μl) was administered 1, 6, 24, 32, 48 and 70 hours before cisternal injection, the expressions of the two ET receptors after day 3 decreased to varying degrees, while the vascular cross-sectional area was significantly higher (P < 0.05). The results suggest that the ET(A)/ET(B) receptors play an important role in cerebral vasospasm after SAH. Application of RO-31-7549 reduced the expression of ET receptors and reduced cerebral vasospasm, suggesting that inhibition of PKC signaling pathway could effectively reduce DCVS after SAH.
Department of Neurosurgery, Binzhou Medical College Affiliated Hospital, Binzhou 256603, PR China.
Leitao
L
Sun
Wensheng
W
Zhang
Xiaohong
X
Wang
Jinning
J
Song
Min
M
Li
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects / Q000502:physiology; D005455:Fluorescent Antibody Technique; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A / Q000096:biosynthesis*; D044023:Receptor, Endothelin B / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013345:Subarachnoid Hemorrhage / Q000378:metabolism*; D020301:Vasospasm, Intracranial / Q000378:metabolism*
D007211:Indoles; D008301:Maleimides; D047428:Protein Kinase Inhibitors; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D011493:Protein Kinase C; C064755:Ro 31-7549