Organic nitrates

Glyceryltrinitrate (GTN), nitroglycerin, isosorbide mononitrate (ISM) and isosorbide dinitrate (IDN) are prodrugs (nitrovasodilators) that are biotransformed within vascular smooth muscle cells via various enzymatic reactions (e.g. mitochondrial aldehyde dehydrogenase, cytochrome P₄₅₀) to yield nitric oxide, which activates soluable guanylyl cyclase thereby stimulating vasodilatation (Fig. 3.11.1). The major action of organic nitrates is venodilatation (capacitance vessels), thereby reducing venous return and preload to the heart. This will reduce myocardial wall tension, oxygen demand, ischaemia and hence pain. Organic nitrates have little vasodilating activity on coronary arteries, particularly if atherosclerosis is present and obstruction is fixed. Vasodilatation of collateral vessels may increase blood flow to the myocardium. While not a major action, nitrates can also reduce total peripheral resistance following dilatation of arterioles (resistance vessels). However, sympathetic reflexes overcome any benefit derived from this mechanism.

Fig.3.11.1 Action of organic nitrates in smooth muscle of blood vessels.