β1-Adrenergic cardiac contractility is increased during early endotoxemic shock: Involvement of cyclooxygenases

LIFE SCIENCES

卷:236

Article

Roul, David¹  Rozec, Bertrand²  Ferron, Marine^1,4  Erfanian, Morteza¹  Persello, Antoine¹  Audigane, Leslie¹  Grabherr, Amandine¹  Erraud, Angelique¹  Merlet, Nolwenn^1,4  Guijarro, Damien²  Muramatsu, Ikunobu³  Lauzier, Benjamin¹  Gauthier, Chantal¹ 

[1] Univ Nantes, CNRS, Inst Thorax, INSERM, Nantes, France

[2] Univ Nantes, CNRS, Inst Thorax, INSERM,CHU Nantes, Nantes, France

[3] Univ Fukui, Sch Med, Fukui, Japan

[4] Montreal Heart Inst, Montreal, PQ H1T 1C8, Canada

关键词: Endocardial endothelium;    Beta-adrenergic receptor;    Vascular;    Rat;    Papillary muscle;    LPS;   

DOI  :  10.1016/j.lfs.2019.116865

来源: Elsevier

【 摘 要 】

Aims: Endothelial dysfunction is one of the earliest symptoms in septic patients and plays an important role in the cardiovascular alterations. However, the endothelial mechanisms involved in the impaired sympathetic regulation of the cardiovascular system are not clear. This study aimed to determine the role of the endocardial endothelium (EE) in the cardiac beta-adrenergic (beta-AR) remodeling at the early phase of endotoxemic shock. Main methods: Rats received either lipopolysaccharide (LPS) or saline (control) intravenously. Three hours later, beta-AR cardiac contractility was evaluated on papillary muscles with or without a functional EE. Key findings: Isoproterenol-induced contractility was strongly increased in papillary muscles from LPS rats. A similar increase was observed with a beta 1-AR stimulation, whereas beta(2)-AR and beta(3)-AR produced similar contractility in control and LPS treatments. The removal of the EE did not modify beta(1)-AR-induced contractility in controls, whereas it abolished the increased beta(1)-AR response in LPS-treated muscles. In LPS-treated papillary muscle, the increased beta(1)-AR-induced contractility was not modified by pretreatment with a NOS inhibitor or an endothelin receptor antagonist. Conversely, the increased beta(1)-AR-induced contractility was abolished by indomethacin, a non-selective cyclooxygenase (COX) inhibitor, as well as by selective inhibitors of COX1 and COX2. An early treatment with indomethacin improved the survival of LPS rat. Significance: Our results suggest that the EE is involved in the increased cardiac beta(1)-AR contractility in the early phase of endotoxemic shock. This effect is mediated through the activation of COX1 and COX2 and suggests these may be novel putative therapeutic targets during endotoxemic shock.

【 授权许可】

Free