Myocardial dysfunction in the septic rat heart: role of nitric oxide.
Previous studies have demonstrated that sepsis, endotoxin, and cytokine administration cause myocardial dysfunction. Nitric oxide has been implicated in this dysfunction, since in isolated cardiac tissues, dysfunction is prevented when nitric oxide synthase (NOS) inhibitors are present. To determine whether nitric oxide produced by the inducible form of the enzyme (iNOS) contributed to Escherichia coli sepsis-induced myocardial dysfunction, the effects of preventing the induction of the enzyme or inhibiting the activity of the enzyme were determined. Rats, made septic by the injection of E. coil into the dorsal subcutaneous space, demonstrated a decreased intrinsic contractile function when hearts were studied the next day. Perfusion of hearts in vitro with the iNOS inhibitor S-methylisothiourea did not reverse the sepsis-induced contractile dysfunction. However, treatment of animals with S-methylisothiourea or dexamethasone, a glucocorticoid that prevents the synthesis of the iNOS, at the time of induction of sepsis resulted in partial but not complete attenuation of myocardial contractile dysfunction induced by sepsis. Thus, nitric oxide contributed to myocardial dysfunction in an intact animal treated with E. coli but was not the sole factor involved.
McDonough
K H
KH
Department of Physiology, Louisiana State University Medical Center, New Orleans 70119, USA.
Smith
T
T
Patel
K
K
Quinn
M
M
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D003907:Dexamethasone / Q000494:pharmacology; D004927:Escherichia coli Infections / Q000188:drug therapy / Q000378:metabolism; D066298:In Vitro Techniques; D007550:Isothiuronium / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D009566:Nitrates / Q000097:blood; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000097:blood; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D016277:Ventricular Function, Left / Q000187:drug effects*
D009566:Nitrates; D009573:Nitrites; D007550:Isothiuronium; D009569:Nitric Oxide; D003907:Dexamethasone; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; C027744:S-methylisothiopseudouronium