Contractile responses in spontaneously diabetic mice: I. Involvement of superoxide anion in enhanced contractile response of aorta to norepinephrine in C57BL/KsJ(db/db) mice

Abstract

This study investigated the influence of superoxide anion on the norepinephrine (NE)-induced contractile response in spontaneously diabetic mice. In aortic rings with intact endothelium, NE elicited only a slight increase in tension in nondiabetic mice (db/+M), but a much greater dose-dependent contraction in spontaneously diabetic mice (db/db mice). The NE-induced contractile response was significantly reduced by pretreatment with SOD (180 U/ml) in diabetic mice, but not in control mice. The NE-induced contraction was significantly enhanced by pretreatment with diethyldithiocarbamic acid (DETCA, 10 −3 M), a Cu/Zn SOD inhibitor, in control mice, but not in diabetic mice. The dose–response curve for the acetylcholine-induced relaxation was slightly, but significantly attenuated in diabetic mice. When aortic rings from control mice were incubated with a mixture of hypoxanthine (10 −5 M), xanthine oxidase (0.1 U/ml) and catalase (1000 U/ml) in control mice, they gradually contracted. This contraction was abolished by pretreatment with SOD (180 U/ml) or indomethacin (10 −5 M) or by removal of the endothelium. The enhanced NE-induced dose-dependent contraction seen in diabetic mice was markedly attenuated by indomethacin. These results suggest that in db/db diabetic mice, superoxide anion, perhaps via vasoconstrictor prostanoids, may enhance the contraction induced by NE.