Normalizing Plasma Renin Activity in Experimental Dilated Cardiomyopathy: Effects on Edema, Cachexia, and Survival

Int J Mol Sci. 2019 Aug 9;20(16):3886. doi: 10.3390/ijms20163886.


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.

Keywords: aliskiren; cachexia/sarcopenia; dilated cardiomyopathy; edema; heart failure; neprilysin; plasma renin activity.

MeSH terms

  • Amides / therapeutic use*
  • Animals
  • Cachexia / blood
  • Cachexia / complications
  • Cachexia / drug therapy
  • Cardiomyopathy, Dilated / blood
  • Cardiomyopathy, Dilated / complications
  • Cardiomyopathy, Dilated / drug therapy*
  • Disease Models, Animal
  • Edema / blood
  • Edema / complications
  • Edema / drug therapy
  • Female
  • Fumarates / therapeutic use*
  • Heart Failure / blood
  • Heart Failure / complications
  • Heart Failure / drug therapy
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Renin / antagonists & inhibitors*
  • Renin / blood*


  • Amides
  • Fumarates
  • aliskiren
  • Renin