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(Circulation. 2002;105:387.)
© 2002 American Heart Association, Inc.

Basic Science Reports

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

Rong Wu, MD; Daniel Lamontagne, PhD, PharmB; Jacques de Champlain, MD, PhD, FRCPC

From the Research Group on Autonomic Nervous System (R.W., J.D.C.), Department of Physiology, Faculty of Medicine and the Faculty of Pharmacy (D.L.), University of Montreal, Quebec, Canada.

Correspondence to Jacques de Champlain, MD, PhD, Department of Physiology, Faculty of Medicine, University of Montreal, CP 6128, Succursale Centre-ville, Montréal, Québec, Canada. E-mail grsna{at}ere.umontreal.ca

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 (O₂^-) 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 O₂^- 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 O₂^- 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 O₂^- 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.

Key Words: aspirin • superoxide • hypertension • angiotensin II

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