Endogenous and exogenous nitrates and their role in myocardial ischaemia.
1. Although nitrates have been prescribed in patients with angina pectoris for more than a century, their mechanism of action has only been understood recently. 2. The discovery of the endogenous nitrovasodilator nitric oxide, which is formed in endothelial cells by the enzyme nitric oxide synthase, has greatly expanded our knowledge. Nitric oxide, if released from endothelial cells can interact with vascular smooth muscle as well as circulating blood cells such as platelets. Nitric oxide activates soluble guanylate cyclase, which in turn leads to an intracellular increase in cyclic GMP. In vascular smooth muscle, this causes vasorelaxation, in platelets dysaggregation and prevention of platelet adhesion. This protective pathway both reduces the effects of vasoconstrictor substances, can produce profound vasodilation, if activated appropriately and acts as a regulator of platelet-vessel wall interaction. In addition, nitric oxide inhibits the production and action of endothelin, a 21 amino acid vasoconstrictor peptide formed by endothelial cells. 3. Exogenous nitrovasodilators also exert their action by releasing nitric oxide from the molecule. Their action is particularly pronounced in blood vessels with a low basal production of nitric oxide and is enhanced after removal of the endothelium. In coronary artery disease, the formation of endothelium-derived nitric oxide is reduced, its breakdown is increased, but only at later stages, is the action of endogenous and therapeutic nitrates depressed. 4. Hence, nitrates are an appropriate therapeutic tool in patients with coronary artery disease to substitute the effects of the impaired activity of the endothelial L-arginine/nitric oxide pathway.
Lüscher
T F
TF
Department of Medicine, University Hospital, Basel, Switzerland.
D003327:Coronary Disease / Q000188:drug therapy*; D006801:Humans; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D009566:Nitrates / Q000627:therapeutic use*; D009569:Nitric Oxide / Q000502:physiology / Q000627:therapeutic use; D014665:Vasodilator Agents / Q000627:therapeutic use*
D009566:Nitrates; D014665:Vasodilator Agents; D009569:Nitric Oxide