(Circulation. 1998;98:2621-2628.)
© 1998 American Heart Association, Inc.
Basic Science Reports |
Salt Induces Myocardial and Renal Fibrosis in Normotensive and Hypertensive Rats
From the Department of Medicine, University of Melbourne, Austin and Repatriation Medical Center, Heidelberg, and the Morphology Laboratory, Baker Medical Research Institute, Prahran (R.J.D.), Victoria, Australia.
Correspondence to Dr Louise M. Burrell, Department of Medicine, University of Melbourne, Austin and Repatriation Medical Centre, Heidelberg, Victoria 3084, Australia. E-mail burrell{at}austin.unimelb.edu.au
Background—The detrimental effects of high dietary salt intake may not only involve effects on blood pressure and organ hypertrophy but also lead to tissue fibrosis independently of these factors.
Methods and Results—The effect of a normal (1%) or high (8%) sodium chloride diet on myocardial and renal fibrosis was assessed by quantitative histomorphometry in spontaneously hypertensive rats (SHRs) and normotensive Wistar-Kyoto rats (WKYs). The effect of salt on transforming growth factor-ß1 (TGF-ß1) gene expression was assessed by Northern blot hybridization. A high-salt diet from 8 to 16 weeks of age resulted in increased blood pressure and left ventricular and renal hypertrophy in both WKYs and SHRs. Marked interstitial fibrosis was demonstrated in the left ventricle (LV), glomeruli, and renal tubules and in intramyocardial arteries and arterioles but not in the right ventricle. The collagen volume fraction increased significantly after high-salt diet in the LV, intramyocardial arteries and arterioles, glomeruli, and peritubular areas in both WKYs and SHRs. In the kidneys, glomerular and peritubular type IV collagen was also increased. There was overexpression of TGF-ß1 mRNA in the LV and kidneys in both rat strains after a high-salt diet (all P<0.001).
Conclusions—High dietary salt led to widespread fibrosis and increased TGF-ß1 in the heart and kidney in normotensive and hypertensive rats. These results suggest a specific effect of dietary salt on fibrosis, possibly via TGF-ß1–dependent pathways, and further suggest that excessive salt intake may be an important direct pathogenic factor for cardiovascular disease.
Key Words: sodium • diet • collagen • hypertension • growth substances
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