Landiolol Hydrochloride Ameliorates Acute Lung Injury In A Rat Model Of Early Sepsis Through The Suppression Of Elevated Levels Of Pulmonary Endothelin-1

ASU Author/Contributor (non-ASU co-authors, if there are any, appear on document)
Dr.. Chishimba Nathan Mowa, Associate Professor (Creator)
Appalachian State University (ASU )
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Abstract: Among 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 ß-blocker, plays a crucial role in ameliorating and attenuating LPS-induced ALI through modulation of the ET-1 system. Male Wistar rats at 8 weeks of age were ad-ministered with either saline or lipopolysaccharide (LPS) for three hours (3 h) and some of the LPS-administered rats were continuously treated with landiolol for 3 h. ALI was induced by LPS, including levels of both circulatory and pulmonary TNF-a and IL-6 but [PaO2]was significantly decreased. LPS also induced a signi?cant 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-1a.Finally, the treatment of LPS-administered rats with landiolol for 3 h 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-a, IL-6) in both plasma and lung tissues during sepsis, and expression of pulmonary HIF-1a 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.

Additional Information

Chishimba Nathan Mowa, Yujiro Matsuishi , Subrina Jesmin , Satoru Kawano, Sakuramoto Hideaki ,Nobutake Shimojoa, Shila Akhtar, Sohel Zaedi, Tanzila Khatun, Yoshiya Tsunoda, Takumi Kiwamoto ,Nobuyuki Hizawa, Yoshiaki Inoue, Taro Mizutani (2016) "Landiolol Hydrochloride Ameliorates Acute Lung Injury In A Rat Model Of Early Sepsis Through The Suppression Of Elevated Levels Of Pulmonary Endothelin-1" Life Sciences 166 pp.27-33 Version of Record Available From
Language: English
Date: 2016
Acute lung injury, Landiolol hydrochloride Endothelin, Sepsis, Rat model

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