Vasodilatory effects of a salen-manganese complex with potent oxyradical scavenger activities

被引:10
作者
Barandier, C
Boucher, F
Malfroy, B
deLeiris, J
机构
[1] UNIV GRENOBLE 1, GRP PHYSIOPATHOL CELLULAIRE CARDIAQUE, CNRS ESA 5077, F-38041 GRENOBLE 1, FRANCE
[2] EUKARION, BEDFORD, MA USA
关键词
aorta; rat; vascular reactivity; salen-manganese complex; superoxide dismutase activity; catalase activity;
D O I
10.1159/000159201
中图分类号
Q4 [生理学];
学科分类号
071003 ;
摘要
The effects on rat aorta of EUK-8, salen-manganese complex with high superoxide dismutase and catalase activities, were investigated. EUK-8 protected the acetylcholine-induced relaxation of rat aortic rings from inhibition by superoxide anions and reduced H2O2-induced relaxation. Moreover, EUK-8 dose-dependently relaxed rat aorta precontracted with phenylephrine (10(-6) M) and decreased the vascular the of noncontracted aortic rings. The relaxant effect of EUK-8 was significantly potentiated by endothelium abrasion and/or preincubation with N-nitro-L-arginine methyl ester (10(-5) M and 5 x 10(-4) M), an inhibitor of nitric oxide synthase. Indomethacin (10(-5) M) had no effect on the action of EUK-8, showing that it was not dependent on prostacyclin synthesis. Methylene blue (10(-5) M), an inhibitor of soluble guanylate cyclase, partly abolished relaxation induced by EUK-8. Incubation of rat aorta with EUK-8 (10(-4) M) induced an increase in vascular cyclic AMP content. The lack of inhibition by dl-propranolol showed that adenylate cyclase activation by EUK-8 was not mediated through beta-adrenergic receptors. The inhibition of the effects of EUK-8 by tetraethylammonium (10(-2) M) and glibenclamide (10(-5) and 2 x 10(-5) M) showed the implication of potassium channels in the intracellular cascade triggered by EUK-8. The vasorelaxant activity of EUK-8 was neither affected by xanthine oxidase inhibition (incubation with oxypurinol 25 mu M) nor by superoxide anion scavenging (incubation with oxypurinol 125 mu M). Finally, the ligand for EUK-8 (EUK-8 without manganese), which has the same aromatic structure as EUK-8 without its antioxidant activities because of the absence of manganese, conversely potentiated phenylephrine-induced contraction of aortic rings. We conclude that the vasorelaxant effect of EUK-8 observed under our experimental conditions is essentially mediated through an activation of adenylate cyclase and soluble guanylate cyclase of smooth muscle cells and is different from a classical antioxidant effect of protection of nitric oxide.
引用
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页码:49 / 57
页数:9
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