231: At early phase of endotoxemic shock the increased β-adrenergic contractility is dependent of the endothelial β1-adrenoceptor

Abstract

Cardiovascular alterations in the septic shock include an hypotension associated with a cardiomyopathy. The sympathetic regulation of the cardio-vascular system is impaired during the shock and associated with an altered endothelial function. However, involved cellular mechanisms are not clear. The aims of this project were to determine the role of the three β-adrenoceptor subtypes, β 1 , β 2 and β 3 -AR in the cardiac dysfunction in endotoxemic rats. Rats (12w) received either endotoxin (LPS, 5mg. kg -1 ) or saline i.v. (C). 3h later, cardiac parameters were studied in vivo by echocardiography. Selective β-AR responses were studied on papillary muscle contractility with or without a functional endothelium. Endothelium damage was realized with 3s Triton X-100 at 0.5%. In vivo , LPS rats presented altered systolic (shortening fraction -21±4% vs C p<0.05) and diastolic (E wave -47±4% vs C p<0.05) functions. In papillary muscle, isoproterenol (non selectif βAR agonist) induced contractility was increased in LPS (+105±21% vs C; p<0.05). This increase did not result from β 3 -AR and β 2 -AR because there expressions were respectively decreased by 20±4%; (p<0.05 vs C) and 47±7% (p<0.05 vs C) in LPS and correlated to a maintained β 3 -AR-induced contractility and a decreased β 2 -AR (-38±8% vs C; p<0.05). The β 2 -AR-induced contractility was not modified in LPS muscle without endothelium whereas it was reduced in C muscle without endothelium (79±6% vs C; p<0.05). Conversely, albeit β 1 -AR expression was decreased (-66±5% vs C; p<0.05), β 1 -AR response was increased in papillary muscles (+94±16% vs C; p<0.05) from LPS rats. Surprisingly, the disrupted endothelium abolished this increase. Our results demonstrate, for the first time, an increased β 1 -AR contractility, on papillary muscle form LPS rats, dependent of the functional endothelium. This suggests that β 1 -AR could be involved in the persistent tachycardia observed in the shock leading to propose β 1 -AR blockers in this disease.