title: Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit.
abstract: Endothelial dysfunctions that include decreased nitric oxide (NO) bioactivity and increased endothelin-1 (ET-1) bioactivity have been considered to be involved in the pathogenesis of cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (SAH). Recent cardiovascular studies have revealed that cyclooxygenase-2 (COX-2) is involved in a disturbance in cross-talk between NO and ET-1. COX-2 expression was detected in the endothelial cells of a spastic artery after experimental SAH; however, the pathophysiological significance of COX-2 in relation to CVS remains unclear. The aim of this study was to investigate the role of COX-2 in relation to NO and ET-1 in the pathogenesis of CVS by using the COX-2 selective inhibitor, celecoxib. In the SAH group, SAH was simulated using the double-hemorrhage rabbit model. In the celecoxib group, SAH was simulated and celecoxib was administered. The basilar artery was extracted on day 5 and examined. The cross-section area of the basilar artery in the celecoxib group was significantly larger than in the SAH group. An increased expression of COX-2, ET-1, and ETA receptor (ETAR), and a decreased expression of endothelial NO synthase (eNOS) were seen in the SAH group. In the celecoxib group compared to the SAH group, expression of COX-2, ET-1, and ETAR were statistically significantly decreased, and eNOS expression was significantly increased. COX-2 might be involved in the pathogenesis of CVS due to up-regulation of ET-1 and ETAR and down-regulation of eNOS, and celecoxib may potentially serve as an agent in the prevention of CVS after SAH.
authors.affiliation: Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Munakata
authors.affiliation: Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Naraoka
authors.affiliation: Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Katagai
authors.affiliation: Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan.
authors.forename: Norihito
authors.initials: N
authors.lastname: Shimamura
authors.affiliation: Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan. ohkuma@hirosaki-u.ac.jp.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ohkuma
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D015854:Up-Regulation / Q000502:physiology; D020301:Vasospasm, Intracranial / Q000209:etiology* / Q000378:metabolism*
chemical_list: D019332:Endothelin-1; D009569:Nitric Oxide; D051546:Cyclooxygenase 2
keywords: Celecoxib; Cerebral vasospasm; Cyclooxygenase-2; Endothelin-1; Nitric oxide; Subarachnoid hemorrhage