Dietary salt exacerbates isoproterenol-induced cardiomyopathy in rats

Toxicol Pathol. 2011 Oct;39(6):925-37. doi: 10.1177/0192623311416373. Epub 2011 Aug 30.


Spontaneously hypertensive heart failure rats (SHHFs) take longer to develop compensated heart failure (HF) and congestive decompensation than common surgical models of HF. Isoproterenol (ISO) infusion can accelerate cardiomyopathy in young SHHFs, while dietary salt loading in hypertensive rats induces cardiac fibrosis, hypertrophy, and--in a minority-congestive HF. By combining ISO with dietary salt loading in young SHHFs, the authors sought a nonsurgical model that is more time--and resource-efficient than any of these factors alone. The authors hypothesized that salt loading would enhance ISO-accelerated cardiomyopathy, promoting fibrosis, hypertrophy, and biochemical characteristics of HF. SHHFs (lean male, 90d) were infused for 4 wk with ISO (2.5 mg/kg/day) or saline. After 2 wk of infusion, a 6-wk high-salt diet (4%, 6%, or 8% NaCl) was initiated. Eight percent salt increased heart weight, HF markers (plasma B-type natriuretic peptide, IL-6), lung lymphocytes, and indicators of lung injury and edema (albumin and protein) relative to control diet, while increasing urine pro-atrial natriuretic peptide relative to ISO-only. High salt also exacerbated ISO-cardiomyopathy and fibrosis. Thus, combining ISO infusion with dietary salt loading in SHHFs holds promise for a new rat HF model that may help researchers to elucidate HF mechanisms and unearth effective treatments.

MeSH terms

  • Animals
  • Atrial Natriuretic Factor / urine
  • Biomarkers / analysis
  • Bronchoalveolar Lavage Fluid / chemistry
  • Cardiomyopathies / chemically induced
  • Cardiomyopathies / pathology*
  • Fibrosis
  • Heart / drug effects
  • Heart / physiopathology*
  • Heart Failure / chemically induced
  • Heart Failure / pathology
  • Interleukin-6 / blood
  • Isoproterenol / toxicity*
  • Male
  • Natriuretic Peptide, Brain / blood
  • Rats
  • Rats, Inbred SHR
  • Sodium Chloride, Dietary / administration & dosage*


  • Biomarkers
  • Interleukin-6
  • Sodium Chloride, Dietary
  • Natriuretic Peptide, Brain
  • Atrial Natriuretic Factor
  • Isoproterenol