循環器疾患の臓器連関におけるNO合成酵素系の保護的役割

• Published in: 日本薬理学会年会要旨集 p. 1-S06-3
• Main Author: 筒井, 正人
• Format: Journal Article
• Language: Japanese
• Published: 公益社団法人 日本薬理学会 2022
• Subjects: nitric oxide synthase
• ISSN: 2435-4953
• DOI: 10.1254/jpssuppl.95.0_1-S06-3

The roles of the nitric oxide synthases system (NOSs) in inter-organ communication of cardiovascular diseases remain elusive. In this symposium, we introduce our three studies in which we examined this issue in our mice lacking all three NOS isoforms (triple n/i/eNOSs-/- mice) (PNAS 2005).There is no experimentally useful model that develops myocardial infarction (MI). We previously reported that our triple NOSs-/- mice spontaneously develop MI. However, it takes a long time (1 year) to develop MI (Circulation 2008). We then revealed that 2/3-nephrectomized triple NOSs-/- mice suddenly die due to early onset of MI with high incidence, succeeding in an experimentally useful model of developing MI. These results suggest the protective role of NOSs in reno-cardiac communication (JMCC 2014).We studied the role of bone marrow (BM) NOSs in vascular lesion formation. Constrictive vascular remodeling and neointimal formation at 2 weeks after carotid artery ligation were markedly accelerated in wild-type (WT) mice transplanted with triple NOSs-/- BM as compared with those with WT BM. These results suggest the protective role of NOSs in BM-vascular communication (Nitric Oxide 2011).We investigated the role of NOSs in pulmonary hypertension (PH). The extents of PH at 3 weeks after hypoxic exposure were markedly exacerbated in WT mice transplanted with triple NOSs-/- BM as compared with those with WT BM, suggesting the protective role of NOSs in BM-lung communication (AJRCCM 2018).These lines of evidence indicate the protective role of NOSs in inter-organ communication.