Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries

To investigate the long-term influence of insulin resistance and hyperinsulinemia on vascular reactivity, both muscarinic and α2-receptor-mediated relaxations and the contribution of nitric oxide to these mechanisms were studied in the fructose-fed rat. Male Sprague-Dawley rats were fed either fructose-rich chow (FFR, n = 6) or normal chow (CNT, n = 6) for 40 weeks. Systolic blood pressure was measured by tail-cuff method. A 3-mm segment of mesenteric artery was excised, cannulated and pressurized, pretreated with prazosin (10−6 mol/L) and propranolol (3 × 10−6 mol/L), then precontracted with serotonin (10−6 mol/L). Endothelium dependent relaxation was induced by addition of acetylcholine (10−9 to 10−4 mol/L), or a selective α2-agonist B-HT 920 (10−9 to 10−5 mol/L), with or without the nitric oxide synthase inhibitor L-NAME (10−4 mol/L). Systolic blood pressure was significantly higher in FFR at the early period; however, there was no difference at the end of 40 weeks compared to CNT. Fasting plasma insulin was much higher in FFR than in CNT (110 ± 62 v 41 ± 11 μU/mL, P< .05), whereas plasma glucose was not different. Maximum relaxation to acetylcholine was attained at 10−6 mol/L in FFR but at 3 × 10−7 mol/L in CNT. The degree of maximum relaxation attained with acetylcholine was similar in FFR and CNT (89 ± 9 and 94 ± 4% of precontraction), although attenuated (P< .01) by the addition of L-NAME only in FFR (to 34 ± 22%, P< .05) but not in CNT (to 82 ± 25%). The half-maximal relaxation dose of acetylcholine was greater in FFR (P< .01) compared with CNT and was significantly increased (P< .05) by L-NAME in both groups. B-HT 920 at 10−5 mol/L induced a greater relaxation in CNT (36 ± 10% of serotonin constriction) than in FFR (19 ± 14%, P< .05). These responses were significantly blunted by L-NAME. Thus, muscarinic receptor-mediated vascular relaxation is less sensitive and more nitric oxide dependent in FFR versus CNT. α2-Adrenergic-mediated relaxation, predominantly mediated by nitric oxide, is also impaired in FFR. It is possible that prolonged insulin resistance and hyperinsulinemia in FFR could alter endothelial-dependent vasodilatory mechanisms, thereby contributing to the increase in blood pressure seen in this model.