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The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure
Citation:
CARLL, A. P., N. HAYKAL-COATES, D. W. WINSETT, M. S. HAZARI, A. NYSKA, J. E. RICHARDS, D. L. COSTA, AND A. FARRAJ. The Influence of a High Salt Diet on a Rat Model of Isoproterenol-Induced Heart Failure. Presented at Annual Society of Toxicology, Baltimore, MD, March 15 - 19, 2009.
Impact/Purpose:
We used isoproterenol (ISO) and/high salt diet to accelerate heart failure onset in SHHF rats. We found ISO induced 29% premature mortality associated with increased markers of acute cardiac injury. Among surviving SHHF rats, ISO and salt separately exacerbated cardiomyopathy without affecting markers of acute cardiac injury, but their combined effects on cardiac tissue remain unclear.
Description:
Rat models of heart failure (HF) show varied pathology and time to disease outcome, dependent on induction method. We found that subchronic (4 weeks) isoproterenol (ISO) infusion exacerbated cardiomyopathy in Spontaneously Hypertensive Heart Failure (SHHF) rats. Others have shown that dietary salt loading induces HF in spontaneously hypertensive (SH) rats without acute injury. We hypothesized that ISO and salt combined would induce injury and more overt HF in SHHF rats than either treatment alone. Rats (male, 90d) were infused for 4 weeks with ISO (2.5mg/kg/d s.c.) or saline via osmotic pump. Starting 2 weeks into the infusion regimen, rats were fed high-salt diets (4, 6, or 8% NaCl) for 6 weeks. We previously reported that relative to the control diet, the 8% salt diet increased heart mass, heart failure markers (plasma B-type natriuretic peptide, IL-6), lung lymphocytes, and indicators of lung injury and edema (bronchoalveolar albumin and protein), while it increased urine pro-atrial natriuretic peptide relative to ISO treatment. In the present study we examined the cardiac effects of ISO and salt diet on histopathology and markers of acute injury. ISO caused 29% lethality while high-salt diet had no effect on mortality. ISO-treated rats that died prematurely had elevated serum levels of heart fatty acid-binding protein (H-FABP) and cardiac troponin I (cTnI). At 4 weeks post-infusion, there was no effect of ISO and/or salt diet on cTnI or H-FABP. Preliminary histopathologic analysis indicates that high salt diet may have exacerbated cardiomyopathy in normal SHHF rats, but the effects of salt on ISO-treated SHHFs was unclear. Further examination of physiologic and histologic effects may conclusively determine if a high salt diet exacerbates ISO-induced heart failure in the SHHF rat. (Abstract does not reflect EPA policy; Supported by UNC/EPA CR83323601.)