Salt induces myocardial and renal fibrosis in normotensive and hypertensive rats

Background-The detrimental effects of high dietary salt intake may not only involve effects on blood pressure and organ hypertrophy but also lead to t issue fibrosis independently of these factors. Methods and Results-The effect of a normal (1%) or high (8%) sodium chlorid e diet on myocardial and renal fibrosis was assessed by quantitative histom orphometry in spontaneously hypertensive rats (SHRs) and normotensive Wista r-Kyoto rats (WKYs). The effect of salt on transforming growth factor-beta( 1) (TGF-beta(1)) gene expression was assessed by Northern blot hybridizatio n. A high-salt diet from 8 to 16 weeks of age resulted in increased blood p ressure and left ventricular and renal hypertrophy in both WKYs and SHRs. M arked interstitial fibrosis was demonstrated in the left ventricle (LV), gl omeruli, and renal tubules and in intramyocardial arteries and arterioles b ut not in the right ventricle. The collagen volume fraction increased signi ficantly after high-salt diet in the LV, intramyocardial arteries and arter ioles, glomeruli, and peritubular areas in both WKYs and SHRs. In the kidne ys, glomerular and peritubular type IV collagen was also increased. There w as overexpression of TGF-beta(1) mRNA in the LV and kidneys in both rat str ains after a high-salt diet tall P<0.001). Conclusions-High dietary salt led to widespread fibrosis and increased TGF- beta(1) in the heart and kidney in normotensive and hypertensive rats. Thes e results suggest a specific effect of dietary salt on fibrosis, possibly v ia TGF-beta(1)-dependent pathways, and further suggest that excessive salt intake may be an important direct pathogenic factor for cardiovascular dise ase.