Mechanisms underlying attenuated contractile response of aortic rings to noradrenaline in fructose-fed mice.
We hypothesized that an impairment of endothelial dysfunction and an increased response to alpha-adrenoceptor agonists may occur in fructose-fed, insulin-resistant mice. The aim of the present study was to assess the relationship between endothelial dysfunction and agonist-induced contractile responses in such mice. The acetylcholine-induced relaxation was significantly attenuated in streptozotocin-diabetic and fructose-fed mice. The contractile response to noradrenaline was significantly weaker than the control in fructose-fed but not in streptozotocin-diabetic mice; treatment with N(G)-nitro-L-arginine effectively restored this response. Incubating aortic rings with noradrenaline increased the NO(x) [nitrite (NO(2)(-)) and nitrate (NO(3)(-))] level and this level was significantly higher in fructose-fed mice than in control mice. Clonidine induced a dose-dependent relaxation in aortic rings pre-contracted with prostaglandin F(2alpha) that was completely abolished by N(G)-nitro-L-arginine; this relaxation was markedly enhanced in fructose-fed mice. In both control and fructose-fed mice, the clonidine-induced relaxation was significantly attenuated and the noradrenaline-induced contraction augmented by pertussis toxin. These results suggest that endothelial function is attenuated in both fructose-fed and streptozotocin-diabetic mice. It is suggested that the decreased noradrenaline contractile response in fructose-fed mice (compared to both controls and streptozotocin-diabetic mice) may be due to an increase in nitric oxide formation mediated by endothelial GTP-binding-coupled alpha(2)-adrenoceptors.
Kamata
K
K
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa, Tokyo, 142-8501, Japan. kamata@hoshi.ac.jp
Kanie
N
N
Inose
A
A
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002784:Cholesterol / Q000097:blood; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D003000:Clonidine / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000097:blood; D004040:Dietary Carbohydrates / Q000008:administration & dosage; D015237:Dinoprost / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000008:administration & dosage*; D066298:In Vitro Techniques; D007328:Insulin / Q000097:blood; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D009566:Nitrates / Q000378:metabolism; D009573:Nitrites / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology*; D037342:Pertussis Toxin; D011188:Potassium / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D001786:Blood Glucose; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D004040:Dietary Carbohydrates; D007328:Insulin; D009566:Nitrates; D009573:Nitrites; D014280:Triglycerides; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D009599:Nitroprusside; D005632:Fructose; D012701:Serotonin; D002784:Cholesterol; D015237:Dinoprost; D037342:Pertussis Toxin; D003000:Clonidine; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine