[Pharmacology of nitrates]

Nitrates (nitroglycerin, isosorbide dinitrate and isosorbide 5-mononitrate) are drugs used in the treatment of angina pectoris and in the prevention of myocardial ischaemia. By providing nitric oxide (NO), which, in turn, increases the level of cGMP and decreases (Ca)i, they induce effects of vasodilatation and anti-platelet aggregation. In patients suffering from endothelial dysfunction, they therefore act like exogenous NO providers. At low doses, they act as venous vasodilators by decreasing the tension (preload) and volume of the ventricle, as well as myocardial oxygen requirements (MVO2). The reduction of ventricular tension and volume also indirectly increases subendocardial blood flow. In the coronary vessels, they produce epicardial vasodilatation (all the more marked the smaller the calibre of the vessels), increase collateral blood flow and, through stenoses, induce reduction of coronary tone and the excess pressure due to vasospasm. At higher doses, the vasodilator effect is exerted on arteries and, although it reduces peripheral vascular resistance (afterload) and blood pressure, it can also produce reflex tachycardia which annihilates the reduction of MVO2. Finally, nitrates exert anti-platelet aggregation effects. All these properties account for the beneficial effects of nitrates in acute or chronic coronary ischaemic syndromes, in patients suffering from left ventricular dysfunction, during the acute phase of myocardial infarction and in post-myocardial infarction ventricular remodelling. There are many pharmaceutical formulations allowing administration of nitrates via a variety of routes. However, the efficacy of repeated nitrate administration is limited by the appearance of tolerance, which can be prevented by observing short periods without nitrates (8-24 hours). The use of sustained-release formulations, with a single daily dose, ensures a maximum anti-ischaemic effect, reduces the risk of tolerance and facilitates the patient's compliance with treatment, which makes it the treatment of choice in angina patients.