Angiotensin II exacerbates lipopolysaccharide-induced contractile depression in rabbit cardiac myocytes

Satoshi Yasuda, Wilbur Y.W. Lew

Research output: Contribution to journalArticlepeer-review

16 Citations (Scopus)

Abstract

In sepsis, lipopolysaccharide (LPS) depresses cardiac function by inducing production of nitric oxide (NO) and its second messenger cGMP. LPS also stimulates ANG II production. We hypothesized that ANG II modulates the cardiac response to LPS. Adult rabbit cardiac myocytes incubated with LPS (10 ng/ml) had increased cardiac cGMP after 6 h (but not within 1 h) [527 ± 43 vs. 316 ± 27 (SE) fmol/mg protein in controls, n = 16 each group, P < 0.05]. This was associated with depressed cell shortening with no alterations in Ca2+ transients (indo 1 fluorescence), indicating a decreased myofilament responsiveness to Ca2+. ANG II (100 nM) alone had no effect. However, ANG II with LPS produced higher cGMP levels (1,025 ± 113 fmol/mg protein, n = 16, P < 0.05 vs. LPS alone), more severe contractile depression, impaired Ca2+ handling, and decreased mitochondrial activity (MTS assay). We conclude that ANG II and LPS have synergistic effects on the activation of NO-cGMP pathways to induce dose-dependent impairments in excitation- contraction coupling in cardiac myocytes.

Original languageEnglish
Pages (from-to)H1442-H1449
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume276
Issue number5 45-5
DOIs
Publication statusPublished - 1999 May
Externally publishedYes

Keywords

  • Contractility
  • Guanosine 3',5'-cyclic monophosphate
  • Intracellular calcium
  • Sepsis

ASJC Scopus subject areas

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

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