Comparison of terbutaline and dobutamine in rats with endotoxemia

It is generally accepted that bacterial endotoxin (lipopolysaccharide, LPS) acts via endogenous mediators leading to endotoxicity. Among these endogenous mediators, tumor necrosis factor-alpha (TNF-alpha) seems to induce all characteristics for endotoxemia. Inhibition of TNF-(alpha production by cAMP-elevating agents has been well documented. Terbutaline (an agonist of beta2-adrenoceptor) and dobutamine (an agonist of beta1-adrenoceptor), both are able to increase intracellular cAMP via activation of adenylate cyclase, were examined in the anesthetized rat with endotoxemia. Terbutaline or dobutamine was administered to the rat at 30 min after LPS injection. Hemodynamic changes and plasma TNF-alpha and nitrate (the end product of nitric oxide [NO]) levels as well as superoxide anion (O2*-) production in the aorta were examined in this study. Results showed that terbutaline, but not dobutamine, improved the circulatory failure (e.g. hypotension and vascular hyporeactivity) in rats with endotoxemia. In addition, both terbutaline and dobutamine reduced the plasma TNF-alpha level, but only terbutaline attenuated the aortic O2*- production in these endotoxemic rats. The beneficial effect of terbutaline in endotoxemic animals was associated with a reduction in plasma TNF-alpha and aortic O2*-, but not in plasma NO.