title: Impaired endothelial alpha-2 adrenergic receptor-mediated vascular relaxation in the fructose-fed rat.
abstract: 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.
authors.affiliation: Department of Veteran's Affairs Greater Los Angeles Healthcare System, Sepulveda Ambulatory Care Center, CA 91343, USA.
authors.forename: Yoshitoki
authors.initials: Y
authors.lastname: Takagawa
authors.forename: Morris E
authors.initials: ME
authors.lastname: Berger
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tuck
authors.forename: Michael S
authors.initials: MS
authors.lastname: Golub
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001381:Azepines / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004032:Diet; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism*; D005632:Fructose / Q000008:administration & dosage* / Q000494:pharmacology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology*
chemical_list: D000316:Adrenergic alpha-Agonists; D001381:Azepines; D011942:Receptors, Adrenergic, alpha; D005632:Fructose; C024763:talipexole