Dietary Salt Exacerbates Isoproterenol-Induced Cardiomyopathy in Rats

• Published in: Toxicologic pathology 2011-10, Vol.39 (6), p.925-937
• Main Authors: Carll, Alex P., Haykal-Coates, Najwa, Winsett, Darrell W., Hazari, Mehdi S., Nyska, Abraham, Richards, Judy H., Willis, Monte S., Costa, Daniel L., Farraj, Aimen K.
• Format: Article
• Language: English
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Atrial Natriuretic Factor - urine; Biological and medical sciences; Biomarkers - analysis; Blood and lymphatic vessels; Bronchoalveolar Lavage Fluid - chemistry; Cardiology. Vascular system; Cardiomyopathies - chemically induced; Cardiomyopathies - pathology; Fibrosis; Heart; Heart - drug effects; Heart - physiopathology; Heart Failure - chemically induced; Heart Failure - pathology; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Interleukin-6 - blood; Isoproterenol - toxicity; Male; Medical sciences; Myocarditis. Cardiomyopathies; Natriuretic Peptide, Brain - blood; Rats; Rats, Inbred SHR; Sodium Chloride, Dietary - administration & dosage; Toxicology
• ISSN: 0192-6233; 1533-1601
• DOI: 10.1177/0192623311416373

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.