Allopurinol Reduces Neointimal Hyperplasia in the Carotid Artery Ligation Model in Spontaneously Hypertensive Rats

Abstract

Uric acid and oxidative stress promote cardiovascular diseases, including atherosclerosis and hypertension. Xanthine oxidase, through which uric acid is generated, is a free-radical generating enzyme. The aim of the current study was to investigate whether allopurinol, an inhibitor of xanthine oxidase activity, affects vascular remodeling and vascular smooth muscle cell (VSMC) proliferation. In the carotid artery ligation model using spontaneously hypertensive rats (SHR), treatment with allopurinol induced a reduction in the neointima/media ratio by 27% (38.5±34.3% in the control group and 28.1±20.8% in the allopurinol-treated group, respectively, ppin vitro study, high concentrations of uric acid (100 and 200 μmol/l) stimulated VSMC growth, but there was no stimulation of these cells by a low concentration of uric acid (50 μmol/l) or by any of three concentrations of xanthine (50, 100 and 200 μmol/l). In addition, allopurinol (5 μmol/l) had no effect on the cell growth. In conclusion, uric acid is a potent stimulator of VSMC proliferation, and allopurinol prevented vascular remodeling in SHR at least in part by inhibiting uric acid concentration.