Superoxide dismutase entrapped-liposomes restore the impaired endothelium-dependent relaxation of resistance arteries in experimental diabetes.
Diabetes is associated with impaired endothelium-dependent relaxation. We questioned whether administration of superoxide dismutase (superoxide: superoxide oxidoreductase, EC 1.15.1.1) entrapped in long-circulating liposomes improves the vascular reactivity of the resistance arteries. Using the myograph technique, the vasodilation in response to acetylcholine was measured in mesenteric resistance arteries isolated from diabetic or normal hamsters treated for 3 days with superoxide dismutase entrapped in liposomes, with the same concentrations of free superoxide dismutase and plain liposomes, or untreated. Superoxide dismutase activity and nitric oxide (NO) levels were assayed by spectrophotometry, superoxide dismutase levels by Western blot and the role of N(pi)-nitro-L-arginine ethylester (L-NAME) on vasodilation by the myograph technique. Our data revealed that: (i) superoxide dismutase entrapped in liposomes restored to a great extent the endothelium-dependent relaxation of diabetic hamster resistance arteries; (ii) in superoxide dismutase entrapped in liposomes-treated diabetic animals, the activity and the level of superoxide dismutase in arterial homogenates as well as the serum nitrite levels were significantly higher than those in untreated hamsters or hamsters treated with free superoxide dismutase and plain liposomes: (iii) L-NAME inhibited the response of arteries to acetylcholine in superoxide dismutase entrapped in liposomes-treated diabetic hamsters. These results suggest that superoxide dismutase entrapped in liposomes is effective in scavenging superoxide anions, increases nitric oxide bioactivity and improves the vasorelaxation of resistance arteries in diabetic hamsters.
Voinea
Manuela
M
Institute of Cellular Biology and Pathology "Nicolae Simionescu"8, B.P. Hasdeu St., PO Box 35-14, 79691, Bucharest, Romania. mvoinea@simionescu.instcellbiopath.ro
Georgescu
Adriana
A
Manea
Adrian
A
Dragomir
Elena
E
Manduteanu
Ileana
I
Popov
Doina
D
Simionescu
Maya
M
D000818:Animals; D006224:Cricetinae; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000201:enzymology*; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000201:enzymology; D008081:Liposomes; D008297:Male; D008647:Mesocricetus; D013482:Superoxide Dismutase / Q000008:administration & dosage*; D014655:Vascular Resistance / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
D008081:Liposomes; D013482:Superoxide Dismutase