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Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats
Citation:
Carll, A. P., N. HAYKAL-COATES, D. W. WINSETT, M. S. HAZARI, A. Nyska, J. E. RICHARDS, M. Willlis, D. L. COSTA, AND A. FARRAJ. Dietary Salt Exacerbates Isoproterenol-induced Cardiomyopathy in Rats. TOXICOLOGICAL PATHOLOGY. Society of Toxicology, RESTON, VA, 39(6):925-37, (2011).
Impact/Purpose:
High salt diet in conjunction with isoproterenol treatment as demonstrated in the present study offers a particularly promising methodology to induce cardiomyopathy that may progress to sustained cardiac insufficiency. The abbreviated regimen coupled with the absence of surgical procedures may reduce the cost and uncertainties associated with heart failure models and facilitate the elucidation of mechanisms that mediate heart failure as well as its exacerbation with air pollution exposure.
Description:
Spontaneously Hypertensive Heart Failure rats (SHHFs) take far longer to develop compensated heart failure and congestive decompensation than common surgical models of heart failure. 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 heart failure. By combining ISO with dietary salt loading in young SHHFs, we sought a non-surgical heart failure model that is more time-and resource-efficient than any of these factors alone. We hypothesized that salt loading would enhance ISO-accelerated cardiomyopathy, promoting myocardial fibrosis, hypertrophy, and biochemical characteristics of heart failure. Young SHHFs (lean male, 90d) were infused for 4 weeks with ISO (2.5mg/kg/d) or saline. After 2 weeks of infusion, a 6-week high-salt diet (4, 6, or 8% NaCI) was initiated. Eight percent salt increased heart weight, heart failure 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 diet also exacerbated ISO-induced cardiomyopathy and myocardial fibrosis. Thus, combining ISO infusion with dietary salt loading in SHHFs holds promise for a new rat heart failure model that may facilitate the elucidation of HF mechanisms and the discovery of treatments.
