Dietary salt exacerbates isoproterenol-induced cardiomyopathy in rats

Alex P. Carll, Najwa Haykal-Coates, Darrell W. Winsett, Mehdi S. Hazari, Abraham Nyska, Judy H. Richards, Monte S. Willis, Daniel L. Costa, Aimen K. Farraj

Research output: Contribution to journalArticle

4 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)925-937
Number of pages13
JournalToxicologic Pathology
Issue number6
StatePublished - Oct 1 2011
Externally publishedYes


  • cardiomyopathy; salt; isoproterenol; heart failure; spontaneously hypertensive; rats; fibrosis

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology
  • Toxicology
  • Cell Biology

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    Carll, A. P., Haykal-Coates, N., Winsett, D. W., Hazari, M. S., Nyska, A., Richards, J. H., Willis, M. S., Costa, D. L., & Farraj, A. K. (2011). Dietary salt exacerbates isoproterenol-induced cardiomyopathy in rats. Toxicologic Pathology, 39(6), 925-937.