Renna N, Risler N, Cruzado M, Gonzalez S, Lama C, Miatello R M
Dept. of Morphophysiology, School of Medicine, National University of Cuyo and CONICET, Mendoza, Argentina.
Cell Mol Biol (Noisy-le-grand). 2005 Nov 8;51(6):531-7.
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.
奈必洛尔是一种血管扩张剂，它将β-肾上腺素能阻断活性与通过内皮一氧化氮（NO）途径介导的对血管平滑肌细胞（VSMC）的舒张作用相结合。果糖喂养大鼠（FFR）提供了一种饮食诱导的胰岛素抵抗综合征模型，该模型已被用于研究与该综合征相关的病理生理机制。我们的主要目的是研究长期给予奈必洛尔对果糖喂养大鼠（FFR）代谢和心血管变量的影响，在该模型中已经描述了NO生物利用度的改变。雄性Wistar大鼠随机分为4组（每组n = 8）：I. 对照组（C）；II. 对照组 + 奈必洛尔（C+N）：在最后4周期间，饮用水中含1 mg/kg⁻¹×天⁻¹。III. FFR组：大鼠在8周内饮用含10%（w/v）溶液的果糖水，IV. FFR+N组：同II加III。在8周的实验期内，评估收缩压（SBP）、葡萄糖耐量试验（GTT）和血浆硫代巴比妥酸反应性物质（TBARS）的变化。在该实验期结束时，处死大鼠并切除心脏和肾脏，以计算相对心脏重量（RHW）并对肾动脉的管腔与中膜比值（L/M）进行组织学评估。FFR组大鼠的SBP和RHW升高，表现出葡萄糖不耐受和脂质过氧化增加。此外，FFR组肾动脉出现血管重塑，表现为L/M的变化。尽管给予奈必洛尔并未逆转代谢变化，但该药物成功降低了SBP、TBARS水平，并逆转了诸如心脏肥大和肾动脉重塑等结构变化。数据表明，给予奈必洛尔可能参与了与胰岛素抵抗综合征相关的心血管结构变化的逆转。
