Effects of chronic insulin on endothelial dysfunction of basilar arteries from established streptozotocin-diabetic rats.
Our goals were to determine both the effects of chronic insulin treatment on the impaired endothelium-dependent relaxation present in basilar arteries from established diabetic rats and the molecular basis of these effects. Acetylcholine-induced relaxation in basilar artery rings was impaired in the streptozotocin-induced diabetic group, and this impaired response was recovered by insulin treatment. The contraction induced by a nitric oxide synthase inhibitor was decreased in the insulin-untreated diabetic group, but was increased by insulin or NAD(P)H oxidase inhibitor treatment. The manganese-superoxide dismutase (Mn-SOD) mRNA level was significantly lower in basilar arteries from insulin-untreated diabetic rats than in those from the controls, whereas the mRNA for gp91phox, an NAD(P)H oxidase subunit, was increased. In the insulin-treated group, the basilar artery p22phox mRNA level was reduced (vs. insulin-untreated diabetic). These results suggest that the presence of endothelial dysfunction in the diabetic basilar artery is related to increased oxidative stress, and that insulin preserves endothelial function by alleviating oxidative stress. Furthermore, we directly demonstrated that the expression profile for SOD and NAD(P)H oxidase was altered in the streptozotocin-induced diabetic basilar artery.
Matsumoto
Takayuki
T
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
Yoshiyama
Shintaro
S
Wakabayashi
Kentaro
K
Kobayashi
Tsuneo
T
Kamata
Katsuo
K
D000818:Animals; D001488:Basilar Artery / Q000187:drug effects* / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D007328:Insulin / Q000008:administration & dosage*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D007328:Insulin