• Satoko Fuji, Shonosuke Matsushita, Kazuyuki Hyodo, Motoo Osaka, Hiroaki Sakamoto, Kenkichi Tanioka, Kazunori Miyakawa, Misao Kubota, Yuji Hiramatsu, and Chiho Tokunaga.
• School of Medicine, University of Tsukuba, Tsukuba, Japan.
• Gen Thorac Cardiovasc Surg. 2016 Oct 1; 64 (10): 597-603.

ObjectivesPulmonary arterial hypertension (PAH) is a progressive disease which causes increased vascular resistance. In this study, our purpose was to quantify the micro-vascular remodeling in monocrotaline-induced PAH rats using synchrotron radiation pulmonary micro-angiography (SRPA), a method we have previously established in an in vivo rat model. To determine the relationship between endothelial function and vascular remodeling, the local expression of endothelin-1 (ET-1), endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF) was evaluated using immunohistochemical staining.MethodsMonocrotaline-induced PAH rats were created by subcutaneous injection of monocrotaline. After 2 weeks, SRPA was performed at the Photon Factory of the High Energy Accelerator Research Organization. The internal diameters of pulmonary arterioles were measured using SRPA images. Semi-quantified analyses of ET-1, eNOS and VEGF expression in pulmonary arterioles were performed by immunohistochemical staining.ResultsMicro-vascular density and the internal diameters of pulmonary arterioles were significantly decreased in PAH. ET-1 expression was significantly increased in PAH compared with the control (1.53 ± 0.45 vs. 0.80 ± 0.14) and eNOS expression was significantly decreased in PAH compared with the control (1.12 ± 0.59 vs. 1.91 ± 0.66), although VEGF expression did not differ between the groups.ConclusionsSRPA can be effectively used for visualizing the decreased pulmonary micro-vasculature associated with PAH. Increased ET-1 expression and decreased eNOS expression may contribute to the proliferation and vasospasm of pulmonary arterioles induced by endothelial dysfunction due to PAH. This SRPA technology may help to identify a correlation between endothelial function and micro-vasculature remodeling in PAH.

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