This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zubkov, A. Y. Articles by Zhang, J. H. Search for Related Content PubMed PubMed Citation Articles by Zubkov, A. Y. Articles by Zhang, J. H. Related Collections Cerebral Aneurysm, AVM, & Subarachnoid hemorrhage Other Vascular biology

(Stroke. 2001;32:154.)
© 2001 American Heart Association, Inc.

Original Contributions

Relaxant Effect of U0126 in Hemolysate-, Oxyhemoglobin-, and Bloody Cerebrospinal Fluid–Induced Contraction in Rabbit Basilar Artery

Alexander Y. Zubkov, MD, PhD; K. Shadon Rollins, BS; Bennett McGehee; Andrew D. Parent, MD John H. Zhang, MD, PhD

From the Department of Neurosurgery, University of Mississippi Medical Center, Jackson.

Correspondence to John H. Zhang, MD, PhD, Department of Neurosurgery, University of Mississippi Medical Center, 2500 N State St, Jackson, MS 39216-4505. E-mail jzhang{at}neurosurgery.umsmed.edu

Background and Purpose—It has been suggested that mitogen-activated protein kinase (MAPK) is involved in cerebral vasospasm after subarachnoid hemorrhage. The present study was undertaken to explore the inhibitory effect of U0126, a novel MAPK inhibitor, in the contraction of the rabbit basilar artery by 3 spasmogens: hemolysate, oxyhemoglobin, and bloody cerebrospinal fluid (CSF) from patients with vasospasm.

Methods—The contraction and relaxation of rabbit basilar arteries were measured 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 subsequently. (2) In the absence of endothelial cells, U0126 produced an inhibitory effect similar to the contractions induced by hemolysate, oxyhemoglobin, or bloody CSF. (3) U0126 relaxed the sustained contraction induced by hemolysate, oxyhemoglobin, or bloody CSF. (4) Hemolysate, oxyhemoglobin, and bloody CSF enhanced MAPK immunoprecipitation. (5) U0126 reduced MAPK immunoprecipitation induced by hemolysate, oxyhemoglobin, and bloody CSF. (6) Hemolysate, oxyhemoglobin, and bloody CSF significantly increased MAPK activity in the rabbit basilar artery. (7) U0126 abolished the effect of hemolysate, oxyhemoglobin, or bloody CSF on MAPK activation.

Conclusions—This study demonstrated a role of MAPK in the contraction of rabbit basilar arteries by hemolysate, oxyhemoglobin, and bloody CSF. MAPK inhibitor U0126 may be useful in the treatment of cerebral vasospasm.

Key Words: cerebrospinal fluid • hemolysis • oxyhemoglobins • protein kinases • vasospasm • rabbits

This article has been cited by other articles:

				M. Satoh, A. D. Parent, and J. H. Zhang Inhibitory Effect With Antisense Mitogen-Activated Protein Kinase Oligodeoxynucleotide Against Cerebral Vasospasm in Rats Stroke, March 1, 2002; 33(3): 775 - 781. [Abstract] [Full Text] [PDF]