Nitric oxide synthase inhibition does not prevent cardiac depression in endotoxic shock.
Enhanced production of nitric oxide has been implicated in cardiac and vascular dysfunction associated with septic and endotoxic shock. To test this hypothesis, conscious rats were administered endotoxin. 6 h later, the rats were anesthetized, arterial pressure was measured, and hearts were removed for Langendorff perfusion in the absence and presence of .01 microM isoproterenol. Left ventricular developed pressure was 61 +/- 6 mmHg in control rats 39 +/- 5 mmHg in endotoxin-treated rats. Inotropic responses to isoproterenol were unaffected by endotoxin treatment. Administration of nitric oxide synthase (NOS) inhibitors (NG-nitro-L-arginine and aminoguanidine) prior to endotoxin did not improve left ventricular function in endotoxin-treated rats. Dexamethasone pretreatment, however, prevented endotoxin-induced cardiac depression. These results suggest that cardiac depression during endotoxemia is not caused by NOS activation and increased nitric oxide production. Furthermore, the cardioprotectant actions of dexamethasone are not related to its ability to inhibit inducible NOS expression.
Klabunde
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Deborah Research Institute, Browns Mills, New Jersey 08015.
Coston
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D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002303:Cardiac Output, Low / Q000209:etiology / Q000517:prevention & control*; D003907:Dexamethasone / Q000627:therapeutic use*; D006146:Guanidines / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007022:Hypotension / Q000209:etiology / Q000517:prevention & control; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D051381:Rats; D017207:Rats, Sprague-Dawley; D012772:Shock, Septic / Q000188:drug therapy* / Q000503:physiopathology
D006146:Guanidines; D019335:Nitroarginine; D009569:Nitric Oxide; D003907:Dexamethasone; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D007545:Isoproterenol; C004479:pimagedine