Antioxidative Properties of Acetylsalicylic Acid on Vascular Tissues From Normotensive and Spontaneously Hypertensive Rats

Abstract

Background — The mechanisms of the beneficial cardiovascular effects of acetylsalicylic acid (ASA, aspirin) therapy are not completely understood. Oxidative stress and inflammation play important roles in the development of cardiovascular diseases. Methods and Results — In this study, we tested the hypothesis that ASA treatment could reduce superoxide anion (O 2 − ) generation in aortic ring and in cultured aortic smooth muscle cells (SMCs) from normotensive (WKY) and hypertensive (SHRs) rats by means of the Lucigenin-enhanced chemiluminescence method. Although ASA did not show any short-term effect in vitro and in vivo, long-term oral treatment (100 mg/kg/day, 12 days) significantly reduced the basal O 2 − production by 27% and 45% in aorta of normotensive and hypertensive rats, respectively, in association with a reduction of the NAD(P)H oxidase activity in both groups. These effects were dose-dependent from 10 to 100 mg/kg/day. Similar effects were observed in SMCs following long-term incubation (48 hours) with ASA. ASA treatment also completely inhibited the angiotensin II–induced hypertension and O 2 − production. Moreover, ASA treatment significantly improved the impaired aortic relaxation response to acetylcholine and markedly attenuated the age-dependent development of hypertension in SHRs. Conclusion — Long-term ASA treatment in vivo markedly reduced vascular O 2 − production through lowering the NAD(P)H oxidase activity in both normotensive and hypertensive rats. These antioxidative properties of ASA are likely involved in the restoration of aortic vasorelaxation, in the attenuation of the development of hypertension in young SHRs, and in the prevention of hypertension following long-term angiotensin II infusion.