Research Article Alteration of Basilar Artery Rho-Kinase and Soluble Guanylyl Cyclase Protein Expression in a Rat Model of Cerebral Vasospasm following Subarachnoid Hemorrhage Chih-Jen Wang, 1,2 Pei-Yu Lee, 3 Bin-Nan Wu, 3 Shu-Chuan Wu, 1 Joon-Khim Loh, 1,2,4 Hung-Pei Tsai, 5 Chia-Li Chung, 4,5 Neal F. Kassell, 6 and Aij-Lie Kwan 1,2,6 1 Division of Neurosurgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan 2 Department of Neurosurgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 3 Department of Pharmacology, Kaohsiung Medical University, Kaohsiung 807, Taiwan 4 Department of Surgery, Kaohsiung Municipal Hsiao-Kang Hospital, Kaohsiung 812, Taiwan 5 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 807, Taiwan 6 Department of Neurological Surgery, University of Virginia Health System, Charlottesville, VA 22908, USA Correspondence should be addressed to Aij-Lie Kwan; a lkwan@yahoo.com Received 4 February 2014; Revised 7 April 2014; Accepted 7 April 2014; Published 1 June 2014 Academic Editor: John H. Zhang Copyright © 2014 Chih-Jen Wang et al. his is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Background and Purpose. he vasoconstrictor endothelin-1 (ET-1) has been implicated in the pathogenesis of cerebral vasospasm following subarachnoid hemorrhage (SAH). Previous results showed that CGS 26303, an endothelin converting enzyme (ECE) inhibitor, efectively prevented and reversed arterial narrowing in animal models of SAH. In the present study, we assessed the efect of CGS 26303 on neurological deicits in SAH rats. he involvement of vasoactive pathways downstream of ET-1 signaling in SAH was also investigated. Methods. Sprague-Dawley rats were divided into ive groups (=6/group): (1) normal control, (2) SAH, (3) SAH+vehicle, (4) SAH+CGS 26303 (prevention), and (5) SAH+CGS 26303 (reversal). SAH was induced by injecting autologous blood into cisterna magna. CGS 26303 (10 mg/kg) was injected intravenously at 1 and 24 hr ater the initiation of SAH in the prevention and reversal protocols, respectively. Behavioral changes were assessed at 48 hr ater SAH. Protein expression was analyzed by Western blots. Results. Deicits in motor function were obvious in the SAH rats, and CGS 26303 signiicantly improved the rate of paraplegia. Expressions of rho-kinase-II and membrane-bound protein kinase C- and rhoA were signiicantly increased, while those of soluble guanylyl cyclase  1 and  1 as well as protein kinase G were signiicantly decreased in the basilar artery of SAH rats. Treatment with CGS 26303 nearly normalized these efects. Conclusions. hese results demonstrate that the rhoA/rho-kinase and sGC/cGMP/PKG pathways play pivotal roles in cerebral vasospasm ater SAH. I t also shows that ECE inhibition is an efective strategy for the treatment of this disease. 1. Introduction Subarachnoid hemorrhage (SAH) is an important subcate- gory of stroke due to an unacceptably high mortality rate as well as the severe complications it causes, such as cere- bral vasospasm, neurological deicit, and cardiopulmonary abnormality [1]. he potent vasoconstrictor endothein-1 (ET- 1) has been implicated in the pathogenesis of this disease [2]. One strategy to inhibit the biological efect of ET-1 is by means of its receptor antagonists. In fact, various selective and nonselective ET-1 receptor antagonists have been evaluated in animal models of cerebral vasospasm following SAH and in humans with varying degrees of success [3, 4]. An alternative approach to ameliorate the deleterious efects of ET-1 is to suppress the production of this vasoconstrictor by inhibiting endothelin-converting enzyme (ECE), which catalyzes the inal step of ET-1 biosynthesis. CGS 26303 is such an inhibitor [5–8], and it has been shown to prevent and reverse cerebral vasospasm in a rabbit model of SAH [9]. Hindawi Publishing Corporation BioMed Research International Volume 2014, Article ID 531508, 8 pages http://dx.doi.org/10.1155/2014/531508