D Roul1, B Rozec2, G André1, N Merlet1, T Tran Quang1, B Lauzier1, M Ferron1, Y Blanloeil3, G Loirand1, V Sauzeau1, C Gauthier1. 1. l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France. 2. l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; CHU Nantes, Department of Anesthesiology and Intensive Care, Nantes 44000, France. Electronic address: Bertrand.rozec@chu-nantes.fr. 3. CHU Nantes, Department of Anesthesiology and Intensive Care, Nantes 44000, France.
Abstract
BACKGROUND AND PURPOSE: The early management of the cardiovascular dysfunction of septic shock is critical as it is associated with a poor outcome. Although the use of catecholamines is a common therapy in this syndrome, no data are available on the involvement of β-adrenoceptor (β-AR) subtypes and only few studies report an alteration of β-adrenergic-induced vasodilation in septic shock. The purpose of the study was to evaluate vascular β1, β2 and β3-AR expression and function in an endotoxemic rat model. EXPERIMENTAL APPROACH: Endotoxemia was induced in rats by intravenous injection of lipopolysaccharide (LPS). β1, β2 and β3-AR mRNA expression was evaluated by RT-PCR in aorta and vascular β1, β2 and β3-AR responses were determined on conducting (aorta) and/or resistance (mesenteric and renal) arteries by constructing relaxation curves in response to different β-AR agonists. RESULTS: The maximal effect of isoproterenol decreased by 31 to 61% in the three vascular beds of LPS-treated rats compared to controls. In aortas from LPS-treated rats, β1 and β3-AR mRNA expression was decreased and associated to a reduced β1 and β3-induced vasodilation. Conversely, albeit β2-AR mRNA was unchanged, the maximal β2-AR-induced vasodilation increased by 49% in aortas from LPS-treated rats compared to controls. This increase was not affected by endothelium removal but was abolished in the presence of a β2-AR antagonist or an adenylate cyclase inhibitor. CONCLUSIONS: In endotoxemia, β2-AR vasodilation was increased by a potential recruitment of β2-AR located on smooth muscle cells. This study suggests that vascular β2-AR should be a putative new therapeutic target in septic shock.
BACKGROUND AND PURPOSE: The early management of the cardiovascular dysfunction of septic shock is critical as it is associated with a poor outcome. Although the use of catecholamines is a common therapy in this syndrome, no data are available on the involvement of β-adrenoceptor (β-AR) subtypes and only few studies report an alteration of β-adrenergic-induced vasodilation in septic shock. The purpose of the study was to evaluate vascular β1, β2 and β3-AR expression and function in an endotoxemic rat model. EXPERIMENTAL APPROACH: Endotoxemia was induced in rats by intravenous injection of lipopolysaccharide (LPS). β1, β2 and β3-AR mRNA expression was evaluated by RT-PCR in aorta and vascular β1, β2 and β3-AR responses were determined on conducting (aorta) and/or resistance (mesenteric and renal) arteries by constructing relaxation curves in response to different β-AR agonists. RESULTS: The maximal effect of isoproterenol decreased by 31 to 61% in the three vascular beds of LPS-treated rats compared to controls. In aortas from LPS-treated rats, β1 and β3-AR mRNA expression was decreased and associated to a reduced β1 and β3-induced vasodilation. Conversely, albeit β2-AR mRNA was unchanged, the maximal β2-AR-induced vasodilation increased by 49% in aortas from LPS-treated rats compared to controls. This increase was not affected by endothelium removal but was abolished in the presence of a β2-AR antagonist or an adenylate cyclase inhibitor. CONCLUSIONS: In endotoxemia, β2-AR vasodilation was increased by a potential recruitment of β2-AR located on smooth muscle cells. This study suggests that vascular β2-AR should be a putative new therapeutic target in septic shock.
Authors: A Blangy-Letheule; A Persello; S Michelland; V Cunin; F Souab; V Aillerie; J Dhot; A Erraud; J Montnach; M Seve; S Bourgoin-Voillard; B Rozec; M De Waard; B Lauzier Journal: Oxid Med Cell Longev Date: 2021-07-24 Impact factor: 6.543