Increased β2-adrenergic vasorelaxation at the early phase of endotoxemic shock in rats.
OBJECTIVE
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.


METHODS
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.
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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D
Roul
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.
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B
Rozec
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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André
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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Merlet
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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Tran Quang
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
B
B
Lauzier
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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M
Ferron
CHU Nantes, Department of Anesthesiology and Intensive Care, Nantes 44000, France.
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Y
Blanloeil
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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Loirand
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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Sauzeau
l'institut du thorax, INSERM UMR-1087, Nantes 44000, France; CNRS UMR-6291, Nantes 44000, France; Université de Nantes, Nantes 44000, France.
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C
Gauthier
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019446:Endotoxemia / Q000378:metabolism / Q000473:pathology*; D007545:Isoproterenol / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D012772:Shock, Septic / Q000378:metabolism* / Q000473:pathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol
Animal model; Beta-adrenoceptor; Blood vessel; Lipopolysaccharide; Septic shock