Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q9UID3 (FFR)
 233 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To investigate the long-term influence of insulin resistance and hyperinsulinemia on vascular reactivity, both muscarinic and alpha2-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 x 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 alpha2-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 microU/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 x 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. Alpha2-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.
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PMID:Long-term fructose feeding impairs vascular relaxation in rat mesenteric arteries. 1149 99

To investigate the vascular endothelial dysfunction in the insulin resistance syndrome, muscarinic and alpha2-adrenergic 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 (3x10(-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 alpha2-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 alpha2-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 alpha2-adrenergic relaxation may contribute to the development of hypertension and insulin resistance in the FFR.
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PMID:Impaired endothelial alpha-2 adrenergic receptor-mediated vascular relaxation in the fructose-fed rat. 1204 35