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.
Highlights
Angina pectoris, usually due to coronary heart disease, is recognized as a transient retrosternal pain syndrome and characteristic of myocardial ischemia
This loss of the ability of relaxation observed in tolerant vessels highlights, in our model, the phenomenon of treatment failure associated with prolonged use of nitrates
In order to examine any potentiating effect on the NTGinduced relaxations (10-9 to 10-5 M) after H. sabdariffa extract (HSE) preexposure at a final concentration of 5.10-2 mg/ml during 30 min, we compare relaxations in HSE-exposed vessels with those obtained with control
Summary
Usually due to coronary heart disease, is recognized as a transient retrosternal pain syndrome and characteristic of myocardial ischemia. It occurs more readily after 50 years and more frequently favored by risk factors: hypertension, diabetes, dyslipidemia, smoking, obesity, heredity (Stritzke et al, 2009). Prevalence is difficult to quantify and varies by country. It is higher in industrialized countries where it affects about 2% of the population (Carevic et al, 2007). In the treatment of myocardial infarction, the first-line drugs consist of nitrates, including nitroglycerin. Their long-term use is limited by a therapeutic escape or tolerance effect, which decreases the therapeutic efficacy of the drug, compromising the patient's prognosis (Munzel et al, 2005; Daiber et al, 2010a; b; Munzel, 2008)
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