Effects of endothelin and nitric oxide on cardiac muscle functions in experimental septic shock model.

Abstract

We aimed to investigate the possible roles of nitric oxide (NO) and endothelin on the changes of cardiac muscle function in both hyper- and hypodynamic septic shock periods. Cecal ligation and puncture was performed in 50 Wistar albino rats to induce septic shock. Changes in atrium and right ventricle papillary muscle contractions, atrium beat rate, adrenergic and cholinergic responses in these tissues were evaluated in vitro. Atrium beat rate increased in hypodynamic period (p < 0.001) that was reversed by bosentan (p < 0.001) and N(G)-nitro-L-arginine methylester (L-NAME; p < 0.05). Atrium contractions decreased in both hyper- and hypodynamic periods (p < 0.001) that were partially ameliorated by bosentan in both periods (p < 0.01) and only in hypodynamic period by L-NAME (p < 0.001). L-NAME increased papillary muscle contractions in both periods (p < 0.01), but bosentan increased it only in hyperdynamic period (p < 0.01). Bosentan and L-NAME increased potency of isoproterenol on atrium beat rate in both periods and increased carbachol potency on atrium beat rate and atrium contraction amplitude only in hypodynamic period. Bosentan increased atrium contraction response to isoproterenol in hypodynamic period (p < 0.05). Papillary muscle contraction response to isoproterenol increased in hypodynamic period (p < 0.05). L-NAME increased papillary muscle contraction response to carbachol in both periods (p < 0.01, p < 0.05, respectively). These results show that NO and endothelin may play a role in positive inotropic and negative chronotropic effects for atrium in septic shock. Bosentan and L-NAME may change potency and efficacy of isoproterenol and carbachol via upregulation of adrenergic and cholinergic receptors and/or through post receptor factors.