Significant reversal of cardiac upregulated endothelin-1 system in a rat model of sepsis by landiolol hydrochloride

• Published in: Life sciences (1973) Vol. 118; no. 2; pp. 357 - 363
• Main Authors: Seki, Yoshimoto, Jesmin, Subrina, Shimojo, Nobutake, Islam, Md. Majedul, Rahman, Md. Arifur, Khatun, Tanzila, Sakuramoto, Hideaki, Oki, Masami, Sonobe, Aiko, Kamiyama, Junko, Hagiya, Keiichi, Kawano, Satoru, Mizutani, Taro
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 24.11.2014
• Subjects: Animals; Blood Gas Analysis; Disease Models, Animal; Endothelin; Endothelin-1 - blood; Endothelin-1 - metabolism; Heart; Hemodynamics - drug effects; Interleukin-6 - blood; Landiolol hydrochloride; Male; Morpholines - pharmacology; Morpholines - therapeutic use; Myocardium - metabolism; Myocardium - pathology; Rat model; Rats, Wistar; Receptors, Endothelin - genetics; Receptors, Endothelin - metabolism; Sepsis; Sepsis - blood; Sepsis - diagnostic imaging; Sepsis - drug therapy; Sepsis - physiopathology; Tumor Necrosis Factor-alpha - blood; Ultrasonography; Up-Regulation - drug effects; Urea - analogs & derivatives; Urea - pharmacology; Urea - therapeutic use; Heart; Rat model; Sepsis; Endothelin; Landiolol hydrochloride
• ISSN: 0024-3205; 1879-0631
• DOI: 10.1016/j.lfs.2014.04.005

Landiolol hydrochloride, an ultra-short-acting highly cardio-selective β-1 blocker, has become useful for various medical problems. Recent studies have demonstrated that co-treatment with landiolol protects against acute lung injury and cardiac dysfunction in rats of lipopolysaccharide (LPS)-induced systemic inflammation, and was also associated with a significant reduction in serum levels of the inflammation mediator HMGB-1 and histological lung damage. Endothelin (ET)-1, a potent vasoconstrictor, has been implicated in pathogenesis of sepsis and sepsis-induced multiple organ dysfunction syndrome. Here, we investigated whether landiolol hydrochloride can play important roles in ameliorating LPS-induced alterations in cardiac ET system of septic rats. Eight-week-old male Wistar rats were administered LPS only for 3h and the rest were treated with LPS as well as with landiolol non-stop for 3h. At 3h after LPS (only) administration, circulatory tumor necrosis factor (TNF)-α level, blood lactate concentration and percentage of fractional shortening of heart were significantly increased. In addition, LPS induced a significant expression of various components of cardiac ET-1 system compared to control. Finally, treatment of LPS-administered rats with landiolol for 3h normalized LPS-induced blood lactate levels and cardiac functional compensatory events, without altering levels of plasma TNF-α and ET-1. Most strikingly, landiolol treatment significantly normalized various components of cardiac ET-1 signaling system in septic rat. Taken together, these data led us to conclude that landiolol may be cardio-protective in septic rats by normalizing the expression of cardiac vasoactive peptide such as ET, without altering the circulatory levels of inflammatory cytokines.