Endothelin-1 ameliorates contractile depression by lipopolysaccharide in cardiac myocytes

Satoshi Yasuda, Wilbur Y.W. Lew

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

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 N(G)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 μM), 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.

Original languageEnglish
Pages (from-to)H1403-H1407
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume273
Issue number3 42-3
DOIs
Publication statusPublished - 1997
Externally publishedYes

Keywords

  • Contractile function
  • Guanosine 3',5'-cyclic monophosphate
  • Nitric oxide synthase
  • Sepsis

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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