Normalizing plasma renin activity in experimental dilated cardiomyopathy: Effects on edema, cachexia, and survival

Ryan D. Sullivan, Radhika M. Mehta, Ranjana Tripathi, Inna P. Gladysheva, Guy L. Reed

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Heart failure (HF) patients frequently have elevated plasma renin activity. We examined the significance of elevated plasma renin activity in a translationally-relevant model of dilated cardiomyopathy (DCM), which replicates the progressive stages (A–D) of human HF. Female mice with DCM and elevated plasma renin activity concentrations were treated with a direct renin inhibitor (aliskiren) in a randomized, blinded fashion beginning at Stage B HF. By comparison to controls, aliskiren treatment normalized pathologically elevated plasma renin activity (p < 0.001) and neprilysin levels (p < 0.001), but did not significantly alter pathological changes in plasma aldosterone, angiotensin II, atrial natriuretic peptide, or corin levels. Aliskiren improved cardiac systolic function (ejection fraction, p < 0.05; cardiac output, p < 0.01) and significantly reduced the longitudinal development of edema (extracellular water, p < 0.0001), retarding the transition from Stage B to Stage C HF. The normalization of elevated plasma renin activity reduced the loss of body fat and lean mass (cachexia/sarcopenia), p < 0.001) and prolonged survival (p < 0.05). In summary, the normalization of plasma renin activity retards the progression of experimental HF by improving cardiac systolic function, reducing the development of systemic edema, cachexia/sarcopenia, and mortality. These data suggest that targeting pathologically elevated plasma renin activity may be beneficial in appropriately selected HF patients.

Original languageEnglish (US)
Article number3886
JournalInternational journal of molecular sciences
Volume20
Issue number16
DOIs
StatePublished - Aug 2 2019

Keywords

  • Aliskiren
  • Cachexia/sarcopenia
  • Dilated cardiomyopathy
  • Edema
  • Heart failure
  • Neprilysin
  • Plasma renin activity

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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