Relaxant effect of U0126 in hemolysate-, oxyhemoglobin-, and bloody cerebrospinal fluid-induced contraction in rabbit basilar artery

Background and Purpose-It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrh age. The present study was undertaken to explore the inhibitory effect of U 0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar arte ry by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal flu id (CSF) from patients with vasospasm. Methods The contraction and relaxation of rabbit basilar arteries were meas ured by isometric tension. MAPK immunoprecipitation was assessed by Western blot analysis. Results-(1) Pretreatment of the rabbit basilar arteries with U0126 reduced contractions to hemolysate, oxyhemoglobin, or bloody CSF applied subsequent ly. (2) In the absence of endothelial cells, U0126 produced an inhibitory e ffect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysa te, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecip itation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysat e, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in t he rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxy hemoglobin, or bloody CSF on MAPK activation. Conclusions-This study demonstrated a role of MAPK in the contraction of ra bbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK in hibitor U0126 may be useful in the treatment of cerebral vasospasm.