Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes.
Lipopolysaccharide (LPS) induces cardiac depression by activating nitric oxide pathways to increase guanosine 3',5'-cyclic monophosphate (cGMP), a second messenger of nitric oxide. Endothelin-1 (ET-1) may interact with nitric oxide pathways. We hypothesized that ET-1 modulates LPS-induced contractile depression in cardiac myocytes. Adult rabbit cardiac myocytes exposed to LPS (10 ng/ml) developed decreased cell shortening after 6 h, with an increase in cardiac cGMP levels [606 +/- 36 (SE) fmol/mg protein] compared with control myocytes (360 +/- 26 fmol/mg protein, P < 0.05). LPS effects were completely blocked by coincubation with the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (1 mM). Coincubation with ET-1 (10 nM) attenuated the contractile depression and increase in cGMP with LPS (482 +/- 28 fmol/mg protein, P < 0.05 vs. LPS alone). ET-1 alone did not alter cGMP levels (350 +/- 30 fmol/mg protein). ET-1 effects on contractile function were blocked by BQ-123 (10 microM), a selective ET-1 type A receptor antagonist. We conclude that ET-1 ameliorates LPS-induced contractile depression in cardiac myocytes by attenuating LPS effects on nitric oxide-cGMP pathways.
Yasuda
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Department of Medicine, Veterans Affairs San Diego Healthcare System, California, USA.
Lew
W Y
WY
D000818:Animals; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000378:metabolism; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D007700:Kinetics; D008070:Lipopolysaccharides / Q000633:toxicity*; D009200:Myocardial Contraction / Q000187:drug effects*; D009206:Myocardium / Q000166:cytology / Q000378:metabolism; D010456:Peptides, Cyclic / Q000494:pharmacology; D011817:Rabbits; D019323:omega-N-Methylarginine / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D008070:Lipopolysaccharides; D010456:Peptides, Cyclic; D019323:omega-N-Methylarginine; D006152:Cyclic GMP; C072247:cyclo(Trp-Asp-Pro-Val-Leu)