E024: Alterations in agonist-induced vascular reactivity in long-term hyperinsulinemic fructose-fed rats

To investigate the influence of insulin resistance on vascular reactivity, muscarinic and adrenergic responses in small mesenteric arteries and tail arteries were studied in the fructose-fed rat. The contribution of nitric oxide in relaxation mechanisms was also investigated. Male Sprague-Dawley rats were fed either fructose (60%, FFR, n = 6) or normal chow (C, n = 6) for an average of 35 weeks. A mesenteric artery was cannulated and pressurized in a video-imaging instrument. The artery was pretreated with prazosin (10−6 M) and propranolol (3 × 10−6 M) for one hour, and then precontracted with serotonin (5-HT, 10−6 M). Relaxation was induced by addition of acetylcholine (ACh, 10−9 −10−4 M), or a selective α2-agonist B-HT 920 (10−9 − 10−5 M), in the absence or presence of L-NAME (10−4 M). Tail artery was mounted for isometric tension recording. The artery was exposed to increasing frequencies (1-40 pulses/sec for 30 second intervals) of transmural electrical nerve stimulation (TNS) every 10 minutes. Plasma insulin was significantly higher in FFR than in C (219 ± 112 vs 56 ± 26 μU/ml, p < 0.01), while plasma glucose had no significant difference. In mesenteric artery, maximum relaxation (MaxR) to ACh was attained at 10−5 M in FFR but at 10−6 M in C. MaxR was similar in both FFR and C (89 ± 9 and 94 ± 4% of 5-HT constriction) without L-NAME. However, MaxR was attenuated (p < 0.01) with L-NAME only in FFR (to 34 ± 22%) but not in C (to 82 ± 25%), and the change of MaxR by L-NAME was greater (p < 0.05) in FFR than in C. On the other hand, B-HT 920-induced relaxation at 10−5 M was greater (p < 0.05) in C (36 ± 10% of 5-HT constriction) than in FFR (19 ± 14%). These relaxations were significantly blunted by L-NAME (to 6 ± 9 and 7 ± 7%, p < 0.05). TNS-induced contraction of the tail artery was significantly greater in FFR at 1, 2, 4 and 8 pulse/second, and ED50 of TNS-induced contraction was at 4 pulse/second in FFR, while 8 pulse/second in C. Thus, neurogenic adrenergic response was increased while endothelial α2 mechanism was decreased in FFR. We conclude that muscarinic receptor-mediated vascular relaxation was less sensitive and more nitric oxide dependent in FFR.