Key result
ANG II combined with LPS produced higher cGMP levels (1,025 vs 527 fmol/mg protein; P<0.05) and more severe contractile depression in rabbit cardiac myocytes compared to LPS alone.
Angiotensin II exacerbates LPS-induced contractile depression in cardiac myocytes by synergistically activating NO-cGMP pathways.
Answers are grounded in this paper and cite their sources.
Ang II may worsen septic myocyte depression; extends LPS-NO pathways in animals but leaves open human relevance.
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.
No takes yet. Share an insight, caveat, or question.
Yasuda et al. (1999) studied LPS-induced contractile depression. Angiotensin II (ANG II) with Lipopolysaccharide (LPS) vs. LPS alone, ANG II alone, and controls was evaluated on Cardiac cGMP levels (p=<0.05). ANG II combined with LPS produced higher cGMP levels (1,025 vs 527 fmol/mg protein; P<0.05) and more severe contractile depression in rabbit cardiac myocytes compared to LPS alone.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: