Changes in superoxide dismutase mRNA expression by streptozotocin-induced diabetes.
1. Experiments were designed to investigate the involvement of superoxide anions in the attenuated endothelium-dependent relaxation of the rat aorta from streptozotocin (STZ)-induced diabetic rats. 2. The endothelium-dependent relaxation responses to acetylcholine (ACh, 10(-7) M) in helical strips of the aorta precontracted with noradrenaline (NA, 5 x 10(-3) approximately 3 x 10(-7) M) were significantly decreased in STZ-induced diabetic rats. The recovery phase of the relaxation after single administration of ACh in the STZ-induced diabetic rats was more rapid than those in control vessels. 3. Preincubation of aortic strips with superoxide dismutase (SOD, 60 u ml-1) normalized the recovery phase of the relaxation of diabetic aorta after single administration of ACh, whereas catalase (150 u ml-1) or indomethacin (10(-5) M) had no effects on the relaxation. 4. SOD (180 u ml-1) caused relaxation in NA precontracted aortic strips and the degree of the SOD-induced relaxation was significantly greater in diabetic aorta as compared with age-matched control vessels. 5. When the changes in mRNA expressions of Mn-SOD or Cu-Zn-SOD were observed, Mn-SOD mRNA expression was markedly decreased, and Cu-Zn-SOD was slightly decreased in diabetic aorta. 6. These results suggest that the rapid destruction of NO by superoxide anions may occur in the STZ-induced diabetic rats, and this may be due to a decrease in mRNA expression of Mn-SOD or Cu-Zn-SOD.
Kamata
K
K
Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.
Kobayashi
T
T
D000704:Analysis of Variance; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015870:Gene Expression; D008297:Male; D009119:Muscle Contraction; D009126:Muscle Relaxation; D009569:Nitric Oxide / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D013307:Streptomycin; D013482:Superoxide Dismutase / Q000378:metabolism*
D012333:RNA, Messenger; D009569:Nitric Oxide; D013482:Superoxide Dismutase; D013307:Streptomycin