[From Thomas Lauder-Brunton to endogenous nitrates]

While nitrates have been in clinical use for more than 100 years, their mode of action is of rather recent discovery. Nitrates act by the release of the free radical NO (nitric oxide) which stimulates the cyclic guanosine monophosphate as vasodilatator and as inhibitor of platelet function. The endogenous nitrate NO is derived from L-arginine catalyzed by nitric oxide synthase, a recently cloned enzyme. Nitrates and other nitro-vasodilatators act similarly to the endogenous nitrate, whereby a basal release of NO in the vascular wall reduces the effect of nitro-vasodilatators. Therefore, drugs are particularly effective in endothelium-free vessel segments and in veins, where the basal release of NO is low. A recently discovered effect of nitro-vasodilatators is the inhibition of thrombin and angiotensin II-induced production of endothelin. Insofar the L-arginine/NO metabolism acts as an important regulator in the vessel wall and has a protective role in the circulation by its antispastic and antithrombotic principle.