Abstract 80: Role Of Vascular Beta 2-adrenoceptors In Endotoxemic Shock
Although it is known that during endotoxemic shock the use of β-adrenergic agonists can improve organs blood flow independently of cardiac output increase, there is no study in the literature concerning the remodelling of the vascular β-adrenoceptors (β-AR), β1, β2 and β3. Male Sprague-Dawley rats received either 5 mg/kg of lipopolisaccharide (LPS) or the same volume of the vehicle (C) intravenously. Three hours later, the thoracic aorta rings were harvested to perform functional and mRNA expression studies. To take into account the failure of the vascular constriction in sepsis, aortic rings were preconstricted with an appropriate concentration of phenylephrine (α1-adrenergic agonist) in order to obtain 80% of the maximal contraction in both groups. Concentration-relaxation curves were then constructed with several β-AR agonists: isoproterenol (ISO), a non selective agonist; dobutamine (DOBU), salbutamol (SALBU) and SR 58611A (SR) respectively β1-, β2- and β3-AR agonists. The quantification of the three β-AR mRNA subtypes was monitored by real time quantitative RT-PCR in thoracic aorta of 5 rats in each group. Results were expressed in percentage of expression of a reference gene (HPRT, Hypoxanthine PhosphoRibosylTransferase). The relaxation ISO-induced was significant reduced by 29.4% in LPS treated rats. β1- and β3-AR induced-relaxations were also significantly reduced by 18.5 and 32.6% respectively, whereas β2-AR-induced vasore-laxation was not modified (Table⇓). In LPS treated rats, β1- and β3-AR mRNA abundance was significantly reduced by 40 and 64% (p<0.05) respectively, without modification of β2-AR mRNA. In conclusion, our work suggests, for the first time, a differential regulation of the 3 vascular β-AR at the early stage of endotoxemic shock. Moreover, as vascular β2-AR function and mRNA expression are preserved during endotoxemia, it strengthens the putative effect of β2-AR agonists to maintain blood flow in septic shock.