title: Alterations in vascular endothelial function in the aorta and mesenteric artery in type II diabetic rats.
abstract: We used the partial protection exerted by suitable dosages of nicotinamide against the beta-cytotoxic effect of streptozotocin (STZ) to create an experimental diabetic syndrome in adult rats that appears closer to type II diabetes mellitus than other available animal models. The dosage of 230 mg/kg of nicotinamide given intraperitoneally 15 min before STZ administration (65 mg/kg i.v.) yielded animals with hyperglycemia (187.8 +/- 17.8 vs. 103.8 +/- 2.8 mg/dL in controls; P < 0.001) and preservation of plasma insulin levels. This study assessed the relationship between endothelial dysfunction and agonist-induced contractile responses in such rats. In the thoracic aorta, the acetylcholine (ACh) induced relaxation was significantly reduced and the noradrenaline (NA) induced contractile response was significantly increased in diabetic rats compared with age-matched control rats. In the superior mesenteric artery, the ACh-induced relaxation was similar in magnitude between diabetic and age-matched control rats; however, the ACh-induced endothelium-derived hyperpolarizing factor (EDHF) type relaxation was significantly weaker in diabetic rats than in the controls. The phenylephrine (PE) induced contractile response was not different between the two groups. The plasma concentration of NOx (NO2- + NO3-) was significantly lower in diabetic rats than in control rats. We conclude that vasomotor activities in conduit arteries are impaired in this type II diabetes model.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Kentaro
authors.initials: K
authors.lastname: Wakabayashi
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000503:physiopathology*; D001685:Biological Factors / Q000096:biosynthesis / Q000494:pharmacology; D002712:Chlorides / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000150:complications / Q000188:drug therapy; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006943:Hyperglycemia / Q000139:chemically induced / Q000150:complications; D007213:Indomethacin / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007552:Isotonic Solutions / Q000494:pharmacology; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects / Q000503:physiopathology*; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D009536:Niacinamide / Q000009:adverse effects; D009569:Nitric Oxide / Q000031:analogs & derivatives / Q000097:blood; D019335:Nitroarginine / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000494:pharmacology
chemical_list: D001685:Biological Factors; D002712:Chlorides; D007328:Insulin; D007552:Isotonic Solutions; C067410:endothelium-dependent hyperpolarization factor; D009599:Nitroprusside; D010656:Phenylephrine; D019335:Nitroarginine; D009536:Niacinamide; D009569:Nitric Oxide; D012964:Sodium; D000109:Acetylcholine; D011188:Potassium; D009638:Norepinephrine; D007213:Indomethacin