Nebivolol is a
vasodilator that combines beta-
adrenergic blocking activity with a relaxant effect on vascular smooth muscle cells (VSMC) mediated by the endothelial
nitric oxide (NO) pathway. FFR provide a model of dietary-induced
insulin-resistance syndrome, which has been used to study the pathophysiological mechanisms associated with this syndrome. Our main objective was to examine the effect of long-term administration of
nebivolol on metabolic and cardiovascular variables in
fructose-fed rats (FFR), a model in which an altered bioavailability of NO has been already described. Male Wistar rats were randomly assigned to 4 groups (n = 8 each): I. Control (C); II. Control +
nebivolol (C+N): 1 mg/kg(-1) x day(-1) in
drinking water during the last 4 weeks. III. FFR: rats receiving
fructose in
drinking water as
a 10% (w/v)
solution during 8 weeks, and IV. FFR+N: idem II plus III. During the 8 weeks experimental period, variations in systolic blood pressure (SBP),
glucose tolerance test (GTT) and plasma
thiobarbituric acid-reactive substances (
TBARS) were assessed. At the end of this experimental period, rats were killed and heart and kidneys were excised for calculation of relative heart weight (RHW) and histological evaluation of lumen to media ratio (L/M) in renal arteries. Rats from FFR group increased their SBP and RHW, showed
glucose intolerance and an increment in lipid peroxidation. Moreover, FFR showed
vascular remodeling in renal arteries evidenced by changes in L/M. Although the metabolic changes were not reverted by the administration of
nebivolol, this
drug successfully decreased SBP,
TBARS levels and reverted structural changes such as
cardiac hypertrophy and renal arterial remodeling. Data demonstrate that
nebivolol administration could participate in the reversion of cardiovascular structural changes associated with the
insulin-resistance syndrome.