Biological effects of organic nitroesters and their mechanism of action.

Organic nitroesters e.g. glyceryltrinitrate (NTG) are of great clinical importance in the treatment of angina pectoris. The most important of their biological effects is vasodilation of peripheral arteries, peripheral veins and coronary arteries. Other biological effects, of unknown clinical relevance, are effects on myocardial metabolism and on platelet aggregation. In recent years evidences have accumulated that the vasodilating effects of organic nitroesters are mediated via the cGMP-system, although the exact mechanism of activation of the cGMP-producing enzyme guanylate cyclase is still obscure. Further research about this may elucidate the mechanism behind the development of tolerance. Another theory concerning the mechanism behind the vasodilating properties of NTG is that arachidonic acid metabolites are involved. However no clearcut evidences have been presented to support this theory. We show in this paper results indicating that arachidonic acid metabolites are of no importance for the vasodilating effects of NTG, at least not in vitro. NTG has also been shown to decrease the intracellular Ca2+ -concentration, an effect probably mediated via cGMP but the exact underlying mechanism is not yet fully understood.