title: Endothelial dysfunction in the perfused kidney from the streptozotocin-induced diabetic rat.
abstract: The vasodilator effects of acetylcholine were examined in methoxamine-preconstricted perfused kidneys taken from rats with streptozotocin (STZ)-induced diabetes. Acetylcholine-dependent vasodilatation was significantly weaker in STZ-induced diabetic rats than in age-matched controls, and it was completely abolished by treatment with 60 mM K+ plus NG-nitro-L-arginine (L-NNA) plus methylene blue in the control rats and was significantly but not completely inhibited by these treatment in the diabetic rats. Although acetylcholine-induced vasodilation was not affected by indomethacin in control rats, it was attenuated by indomethacin in the diabetic rats. Arachidonic acid-induced vasoconstriction was slightly but significantly increased in the diabetic rats. Acetylcholine increased significantly the level of 6-keto-prostaglandin F1 alpha in the effluent from perfused kidneys from diabetic rats. These results suggest that the endothelium-dependent vasodilatation induced by acetylcholine in the renal vascular bed of age-matched control rats is due to the release of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF), whereas the vasodilatation induced by acetylcholine in the STZ-diabetic kidney also involves prostaglandin I2 as well as NO and EDHF.
authors.affiliation: Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kamata
authors.forename: M
authors.initials: M
authors.lastname: Hosokawa
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000032:analysis / Q000378:metabolism; D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology; D001095:Arachidonic Acids / Q000494:pharmacology; D001685:Biological Factors / Q000032:analysis / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000737:chemistry / Q000187:drug effects / Q000503:physiopathology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000098:blood supply* / Q000737:chemistry / Q000503:physiopathology; D008297:Male; D008729:Methoxamine / Q000494:pharmacology; D008751:Methylene Blue / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000925:Anticoagulants; D001095:Arachidonic Acids; D001685:Biological Factors; D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009599:Nitroprusside; D019335:Nitroarginine; D015121:6-Ketoprostaglandin F1 alpha; D013311:Streptozocin; D009529:Nicardipine; D008729:Methoxamine; D000109:Acetylcholine; D008751:Methylene Blue; D007213:Indomethacin