肺高血圧症の病態形成における1型Na+/Ca2+交換輸送体の関与について

• Published in: 日本薬理学会年会要旨集 p. 2-P2-07
• Main Authors: 喜多, 紗斗美, 田頭, 秀章, 永田, 旭, 喜多, 知, 岩本, 隆宏
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2021
• Subjects: hypertension; smooth muscle; transporter
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.94.0_2-P2-07

The Na+/Ca2+ exchanger type-1 (NCX1) is a bidirectional transporter controlled by membrane potential and transmembrane gradients of Na+ and Ca2+, which plays an important role in intracellular Ca2+ homeostasis and Ca2+ signaling. We found that NCX1 was upregulated in the pulmonary arteries of mice exposed to chronic hypoxia (10% O2 for 4 weeks). In this study, we investigated the pathophysiological role of NCX1 in hypoxia-induced pulmonary arterial hypertension (PAH), using NCX1-heterozygous (NCX1+/−) mice, in which NCX1 expression is reduced by half, and specific NCX1 inhibitors (SEA0400, KB-R7943). After exposure to 10% O2 for 4 weeks, right ventricular systolic pressure (RVSP) and right ventricular (RV) hypertrophy were attenuated in NCX1+/− mice compared with wild-type mice. Furthermore, continuous administration of NCX inhibitors to wild-type mice by osmotic pumps significantly suppressed hypoxia-induced increase in RVSP. SEA0400 also attenuated pulmonary vessel muscularization, with a slight reduction in RV hypertrophy. These findings indicate that the upregulation of NCX1 contributes to the development of hypoxia-induced PAH, suggesting that NCX1 inhibition might be a novel approach for the treatment of PAH.