Affiliations: [a] Department of Pediatrics, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
| [b] Department of Ophthalmology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
| [c] Department of Neurology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, China
Correspondence:
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Corresponding author: Xiang-Yang Tian, Department of Neurology, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300, China. Tel.: +86 13861557349; Fax: +86 0517 84907287; E-mail: cnxiangyangtian@163.com.
Note: [1] Co-first authors.
Abstract: OBJECTIVE:This study aims to study the effect of Rho kinase inhibitor fasudil on the expression endothelin-1 (ET-1) and nitric oxide (NO) in rats with hypoxic pulmonary hypertension (HPH). METHODS:Twenty-four male SD rats were randomly divided into three groups: control group, model group (HPH group) and HPH+fasudil group. The rat HPH model was established by intermittent hypoxia (IH) at atmospheric pressure. Mean pulmonary artery pressure (mPAP), right ventricular hypertrophy index (RVHI), ET-1 and NO levels, and pulmonary vascular structural changes were observed in all groups. RESULTS:MPAP, RVHI and ET-1 levels were significantly higher in HPH group than in control group, while NO was significantly lower than in control group. In addition, mPAP, RVHI and ET-1 were significantly lower in the HPH+fasudil group than in the HPH group. In the HPH group, ET-1 level was significantly and positively correlated with mPAP and RVHI, NO was negatively correlated with mPAP and RVHI levels, and ET-1 level was significantly and negatively correlated with NO level. In the HPH group, pulmonary arteriolar walls were generally thickened, and lumen stenosis was obvious; while after fasudil treatment, pulmonary arteriolar wall thickening and stenosis degree were significantly reduced. CONCLUSION:Fasudil can significantly reduce ET-l level and increase NO level in HPH rats, suppressing the development of pulmonary arterial hypertension.
