P-595: Impaired α2-adrenergic agonist-induced vasorelaxation in fructose-fed rats

To investigate the significance of the duration of the insulin resistance state on endothelium-dependent vascular reactivity, muscarinic and α2-adrenergic receptor-mediated relaxations in small mesenteric arteries were studied in the fructose-fed rat, a model of the insulin resistance syndrome. Male Sprague-Dawley rats were fed either 60 % fructose (FFR) or normal chow as control (CNT) for 8 and 40 weeks. Systolic blood pressure (SBP) was measured periodically by the tail-cuff method. At the end of each study period, arterial blood samples were taken from the abdominal aorta for measurements of plasma triglyceride (TG), glucose and insulin. A 3 mm segment of tertiary branch of the mesenteric artery (250-300 μm in internal diameter) was cannulated with micropipettes and pressurized to 40 mm Hg. The artery was then treated with prazosin (10-6 M) and propranolol (3' 10-6 M) for one hour. Relaxation was induced by cumulative addition of acetylcholine (ACh, 10-9-10-4 M), or a selective α2-agonist B-HT 920 (10-9-10-5 M) to arteries preconstricted by serotonin (5-HT, 10-6 M). SBP in FFR was significantly higher than that in CNT at several points after 12 weeks of fructose feeding. TG was higher in FFR than in CNT (p