Effects of chronic treatment with the spontaneous nitric oxide releaser FK409 on vascular responses in established streptozotocin-induced diabetic rat.
Experiments were designed to investigate the effects of chronic administration of an NO donor, (+/-)-(E)-ethyl-2-[(E)-ethylhydroxyimino]-5-nitro-3-hexeneamide (FK409), on the impairment of the acetylcholine-induced endothelium-dependent relaxations of the aorta, perfused mesenteric arterial bed and perfused kidney that seen in streptozotocin-induced diabetic rats. In aortic strips and in the perfused kidney, the decreased acetylcholine-induced relaxation seen in diabetes was restored to normal by chronic (daily for 4 weeks) administration of FK409 (20 mg/kg or 10 mg/kg, respectively). Acetylcholine increased the NOx (NO2- and NO3-) level in the perfusates from aortic strips, the perfused kidney and the perfused mesenteric arterial bed. These increases were significantly weaker for diabetic rats than for the controls. This effect of diabetes was ameliorated by chronic administration of FK409 (20 mg/kg) in aortic strips and perfused kidney, but not in the perfused mesenteric arterial bed. These results demonstrate that chronic administration of the novel NO releaser FK409 can improve diabetes-impaired endothelium-dependent vasodilatation in the rat aorta and perfused kidney.
Kamata
K
K
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan. kamata@hoshi.ac.jp
Hayashi
T
T
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007668:Kidney / Q000098:blood supply / Q000187:drug effects; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects; D008729:Methoxamine / Q000494:pharmacology; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009566:Nitrates / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000627:therapeutic use*; D009573:Nitrites / Q000378:metabolism; D009574:Nitro Compounds / Q000008:administration & dosage / Q000627:therapeutic use*; D009599:Nitroprusside / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D009566:Nitrates; D020030:Nitric Oxide Donors; D009573:Nitrites; D009574:Nitro Compounds; D009599:Nitroprusside; C061872:FK 409; D008729:Methoxamine; D000109:Acetylcholine