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, p<0.01) without alterations in vascular circumference at 3 weeks after
ligation when compared to the control.
Allopurinol lowered the serum
uric acid concentration (147.0+/-3.6 micromol/l in the control group and 16.1+/-3.6 micromol/l in the
allopurinol-treated group, respectively p<0.01) and
xanthine oxidase activity, but not the blood pressure. In an in vitro study, high concentrations of
uric acid (100 and 200 micromol/l) stimulated VSMC growth, but there was no stimulation of these cells by a low concentration of
uric acid (50 micromol/I) or by any of three concentrations of
xanthine (50, 100 and 200 micromol/l). In addition,
allopurinol (5 micromol/I) 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.