• Yujiro Matsuishi, Subrina Jesmin, Satoru Kawano, Sakuramoto Hideaki, Nobutake Shimojo, Chishimba Nathan Mowa, Shila Akhtar, Sohel Zaedi, Tanzila Khatun, Yoshiya Tsunoda, Takumi Kiwamoto, Nobuyuki Hizawa, Yoshiaki Inoue, and Taro Mizutani.
• Department of Emergency and Critical Care Medicine, Faculty of Medicine, University of Tsukuba, Tsukuba, Ibaraki, Japan. Electronic address: 0326yujiro@gmail.com.
• Life Sci. 2016 Dec 1; 166: 27-33.

AbstractAmong the dysfunctions and pathologies associated with sepsis, the underlying molecular mechanisms of sepsis-induced acute lung injury (ALI) are poorly understood. Endothelin (ET)-1, a potent vasoconstrictor and pro-inflammatory peptide, is known to be involved in the pathogenesis of ALI in a rat model of sepsis. Here, we investigated whether landiolol hydrochloride, an ultra-short-acting β-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8weeks of age were administered with either saline or lipopolysaccharide (LPS) for three hours (3h) and some of the LPS-administered rats were continuously treated with landiolol for 3h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-α and IL-6 but [PaO2] was significantly decreased. LPS also induced a significant increase in levels of pulmonary ET-1 and ET-A receptor, but levels of ET-B receptor, which has vasodilating effects, were remarkably diminished. Further, LPS administration upregulated the pulmonary expression of HIF-1α. Finally, the treatment of LPS-administered rats with landiolol for 3h ameliorated and prevented ALI, normalized the altered levels of pulmonary ET-1 and ET-A receptors. Landiolol also induced significant down-regulation of ET-B receptor in lung tissues in the early hours (phase) of sepsis. However, Landiolol treatment had no effect on the up-regulated inflammatory mediators (TNF-α, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1α also remained unchanged after landiolol treatment. Collectively, these data led us to conclude that landiolol may ameliorate sepsis-induced ALI via the pulmonary ET system.Copyright © 2016. Published by Elsevier Inc.

38 keywords...

hide…