Abstract
To investigate the vascular endothelial dysfunction in the insulin resistance syndrome, muscarinic and α2-adrenargic mediated relaxations were studied in the fructose-fed rat. Male Sprague-Dawley rats were fed either fructose-rich chow (FFR, n =14) or normal chow (CNT, n =13) for 8 weeks. Systolic blood pressure (SBP) was measured by the tail-cuff method. A 3 mm segment of mesenteric artery was cannulated and pressurized, pretreated with prazosin (10-6 mol⁄l) and propranolol (3×10-6 mol⁄l), then pre-contracted with serotonin (10-6 mol⁄l). Endothelium-dependent relaxation was induced by addition of acetylcholine (ACh, 10-9-10-4 mol⁄l) or a selective α2-agonist, B-HT 920 (10-9-10-5 mol⁄l), with or without the nitric oxide (NO) synthase inhibitor, L-NAME (10-4 mol⁄l). SBP was significantly elevated in FFR but not in CNT. Plasma triglyceride in FFT (241±115 mg⁄dl) was significantly (p<0.01) higher than in CNT (84±34 mg⁄dl). Insulin and insulin⁄glucose ratio were higher but not significantly. Plasma glucose was not different between the two groups. In the dose-response curves to ACh, maximum relaxation and ED50 were similar between FFR and CNT. Moreover, L-NAME shifted the dose-response curves similarly to the right in both groups. Dose-response curves to B-HT 920, however, showed less relaxation in FFR than in CNT (p<0.05). B-HT 920-induced relaxations were mostly abolished by L-NAME. It is concluded that endothelial α2-adrenergic relaxation, predominantly mediated by NO, is likely more sensitive to the development of insulin resistance than muscarinic receptor relaxation in this 8-weeks FFR model. This early impairment of endothelial α2-adrenergic relaxation may contribute to the development of hypertension and insulin resistance in the FFR. (Hypertens Res 2002; 25: 197-202)
