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(Hypertension. 2002;39:443.)
© 2002 American Heart Association, Inc.

Scientific Contributions

Implications of Hyperhomocysteinemia in Glomerular Sclerosis in Hypertension

Ningjun Li; Ya-Fei Chen; Ai-Ping Zou

From the Department of Physiology, Medical College of Wisconsin, Milwaukee, and the Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan.

Reprint requests to Ai-Ping Zou, MD, PhD, Department of Physiology, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226. E-mail azou{at}mcw.edu

Hyperhomocysteinemia (hHcys) has been recognized as a new risk factor for cardiovascular diseases independent of plasma lipid levels or other factors. However, it remains unknown whether hHcys is implicated in the target organ damages associated with hypertension. The present study first examined the possible role of hHcys in the development of glomerulosclerosis in Dahl salt-sensitive (DS) hypertensive rats. High-performance liquid chromatography showed that plasma total homocysteine (tHcys) concentration was 7.64±0.29 µmol/L in conscious DS rats on a low salt (0.4% NaCl) diet, which was higher than 5.23±0.25 µmol/L in Dahl salt-resistant normotensive rats. When these rats were exposed to a high salt (4% NaCl) diet, plasma tHcys markedly increased in DS rats (14.7±1.31 µmol/L) but not in Dahl salt-resistant rats (5.34±0.54 µmol/L). An iron chelater, desferrioxamine (0.3 mg/kg IV per day), completely normalized high salt–induced elevations of plasma tHcys and significantly attenuated the sclerotic changes in the glomeruli in DS rats. To further determine whether hHcys has an independent effect in the development of glomerulosclerosis, Sprague-Dawley rats were fed drinking water containing methionine (1 g/kg per day) for 6 weeks to produce hHcys. In these rats, plasma tHcys increased to 12.5±1.9 µmol/L (versus 6.1±2.6 µmol/L in control rats), and the aorta exhibited typical sclerotic changes, but arterial pressure was not altered. Urinary protein excretion increased to 52±2 mg/24 hours (versus 17±2 mg/24 hours in control rats), and the glomerular mesangium was expanded with glomerular hypercellularity, capillary collapse, and fibrous deposition in the rats with hHcys. These results suggest that elevated plasma homocysteine may be an important pathogenic factor for glomerular damage in hypertension independent of arterial pressure.

Key Words: renal disease • glomerulosclerosis • blood pressure • homocysteine

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