title: Endotoxin-induced contractile dysfunction in guinea pig hearts is not mediated by nitric oxide.
abstract: The decreased contraction amplitude of isolated cardiac myocytes from guinea pigs exposed to lipopolysaccharide (LPS) was reported to be partially reversed by nitro-L-arginine methyl ester (L-NAME), an inhibitor of nitric oxide synthase (NOS) [Brady, et al., Am. J. Physiol. 263 (Heart Circ. Physiol. 32): H1963-H1966, 1992]. We have tested the potential involvement of NO formation in LPS-induced cardiac depression in the intact heart. Isolated perfused hearts of LPS-treated guinea pigs (4 mg/kg 4 h before organ removal) displayed a greatly decreased left ventricular pressure (LVP) when compared with untreated controls (48 +/- 11 vs. 93 +/- 18 mmHg, n = 6 hearts each), whereas heart rate and coronary flow were similar. Perfusion of LPS-treated hearts with L-NMMA or L-NAME (100 microM each) at constant flow did not increase LVP (50 +/- 14 and 44 +/- 11, respectively, vs. 52 +/- 14 mmHg). However, coronary resistance increased significantly. There was no difference between LPS-treated and control hearts in venous adenosine release (104 +/- 58 vs. 133 +/- 86 pmol.min-1.g-1). Measurement of the activities of the induced (iNOS) and constitutive forms of NOS revealed that there was no difference in total NOS activity (237 +/- 82 vs. 181 +/- 97 fmol.min-1.mg protein-1. There was no measurable induction of iNOS in the LPS-treated hearts either. Finally, cardiac energy status was studied by 31P nuclear magnetic resonance spectroscopy. There was no difference between LPS-treated and control hearts in myocardial ATP, creatine phosphate, pH, and free ADP (59 +/- 20 vs. 50 +/- 27 microM).(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Institut für Herz- und Kreislaufphysiologie, Heinrich-Heine-Universität Düsseldorf, Germany.
authors.forename: U K
authors.initials: UK
authors.lastname: Decking
authors.forename: C W
authors.initials: CW
authors.lastname: Flesche
authors.forename: A
authors.initials: A
authors.lastname: Gödecke
authors.forename: J
authors.initials: J
authors.lastname: Schrader
mesh_terms: D000227:Adenine Nucleotides / Q000378:metabolism; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism*; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D002531:Cerebellum / Q000201:enzymology; D002851:Chromatography, High Pressure Liquid; D002956:Citrulline / Q000378:metabolism; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology; D004731:Endotoxins / Q000633:toxicity; D004734:Energy Metabolism / Q000187:drug effects; D004790:Enzyme Induction / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity*; D009682:Magnetic Resonance Spectroscopy; D009200:Myocardial Contraction / Q000187:drug effects / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D019001:Nitric Oxide Synthase; D010725:Phosphocreatine / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D016277:Ventricular Function, Left / Q000187:drug effects; D019323:omega-N-Methylarginine
chemical_list: D000227:Adenine Nucleotides; D004731:Endotoxins; D008070:Lipopolysaccharides; D010725:Phosphocreatine; D019323:omega-N-Methylarginine; D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D019331:NG-Nitroarginine Methyl Ester