title: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Selcuk University, Selcuklu, Konya, Turkey drekfarma@hotmail.com.
authors.forename: E K
authors.initials: EK
authors.lastname: Ozer
authors.affiliation: Department of Pharmacology, Faculty of Medicine, Hacettepe University, Sıhhiye, Ankara, Turkey.
authors.forename: A B
authors.initials: AB
authors.lastname: Iskit
mesh_terms: D000818:Animals; D000077300:Bosentan; D002217:Carbachol / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists / Q000494:pharmacology; D016232:Endothelins / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D010210:Papillary Muscles / Q000502:physiology*; D017208:Rats, Wistar; D012772:Shock, Septic / Q000503:physiopathology*; D013449:Sulfonamides / Q000494:pharmacology
chemical_list: D002316:Cardiotonic Agents; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D013449:Sulfonamides; D009569:Nitric Oxide; D002217:Carbachol; D007545:Isoproterenol; D000077300:Bosentan; D019331:NG-Nitroarginine Methyl Ester
keywords: Sepsis; cardiac muscle; endothelin; nitric oxide