Abstract

Treatment failure or tolerance, which rapidly leads to a reduced hemodynamic effects and therapeutic efficacy is the major limitation of long-term use of nitrates, including nitroglycerin (NTG) in the treatment of coronary artery disease. These effects are most often associated with oxidative stress. Thus, in this work, we were interested in the prevention of nitrate tolerance by the antioxidant compounds from Hibiscus sabdariffa L. crude extract, a plant from the Senegalese Pharmacopoeia, rich in polyphenols. Thoracic aorta segments without endothelium were taken from rats and incubated in isolated organ chambers. The vessels were then pre-exposed with the H. sabdariffa polyphenolic extract (HSE, 5.10^-2 g/l) or antioxidants such as N-acetyl cysteine (NAC, 10^-3 M) or vitamin C (VIT C, 10^-2 M), taken as reference. After a 30 min treatment, aortic segments were exposed to NTG (50 μM, 1 h) to induce tolerance state before being contracted to adrenaline (10^-8 to 10^-5 M), and then relaxed with NTG (10^-9 to 10^-5 M). Polyphenols fromH. sabdariffa potentiated the relaxant response to NTG, whatever the state of vascular tolerance; the HSE partially corrected the in vitro nitrate tolerance. This work suggests interesting therapeutic perspectives by improving the response to treatment with nitrates in coronary patients.

Key words: Nitrate tolerance, antioxidant, vascular diseases, therapeutic agents, medicinal plants.