A METHOD FOR DECREASING SUPEROXIDE ANION PRODUCTION AND FOR THE TREATMENT OF DISEASES ASSOCIATED WITH OXIDATIVE STRESS

摘要

The present invention relates to a new method for reducing vascular, cardiac and colonic tissue O2- generation by lowering the NAD(P)H oxidase activity of these tissues in normal and hypertensive subjects using ASA, nimesulide and indomethacin. Although ASA did not show any acute effect in vitro, chronic oral treatment or chronic incubation with ASA significantly lowered the O2- basal or NAD(P)H activated production in aorta and smooth muscle cells from normotensive and hypertensive rats. These effects were dose-dependent and needed more than 3 days to onset in vivo condition. ASA treatment significantly improved the impaired aortic relaxation response to acetylcholine in SHR and significantly attenuated the age-dependent development of hypertension in young SHR. In another model of hypertension and insulin resistance induced by high glucose feeding, which was also found to be associated with a higher production of superoxide anion in tissues from the cardiovascular system, chronic ASA treatment was found to prevent simultaneously the development of hypertension, insulin resistance and the production of superoxide anion. Finally, in another hypertension model induced by the chronic administration of angiotensin II which has the property to activate NAD(P)H oxidase and to enhance the superoxide production in vessels, the concomitant treatment with ASA was also found to simultaneously prevent the development of hypertension and the enhanced superoxide anion production.