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Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit

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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.

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Authors and Affiliations

  1. Department of Neurosurgery, Hirosaki University Graduate School of Medicine, 5 Zaifu-cho, Hirosaki-shi, Aomori-ken, 036-8562, Japan

    Akira Munakata, Masato Naraoka, Takeshi Katagai, Norihito Shimamura & Hiroki Ohkuma

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  1. Akira Munakata
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  2. Masato Naraoka
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  3. Takeshi Katagai
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Correspondence to Hiroki Ohkuma.

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All institutional and national guidelines for the care and use of laboratory animals were followed.

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The authors declare that they have no competing interests.

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Munakata, A., Naraoka, M., Katagai, T. et al. Role of Cyclooxygenase-2 in Relation to Nitric Oxide and Endothelin-1 on Pathogenesis of Cerebral Vasospasm After Subarachnoid Hemorrhage in Rabbit. Transl. Stroke Res. 7, 220–227 (2016). https://doi.org/10.1007/s12975-016-0466-6

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  • DOI: https://doi.org/10.1007/s12975-016-0466-6

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