The Role of Nitric Oxide in Coronary Disease

Abstract

The vascular endothelium is capable of modulating many biological responses through the release of locally derived vasoactive factors.’ One of the most important is nitric oxide, the endothelium-derived relaxing factor (EDRF).² Nitric oxide is synthesized by endothelial cells from the essential amino acid I-arginine by nitric oxide synthase (NOS). Three forms of nitric oxide synthase have been sequenced: a constitutive form from vascular endothelium; a constitutive form from the central nervous system; and an inducible enzyme derived from macrophages in response to cytokines.⁵ Together, these enzymes, through the release of nitric oxide, control a great variety of processes, in both health and disease. Nitric oxide is important as an inhibitor of platelet aggregation, smooth muscle cell proliferation and endothelial-leukocyte interaction.^6,7,8 However, one of the most important actions of nitric oxide is in the regulation of both basal and stimulated arterial tone.^9,10 In response to a number of pharmacological and physiological stimuli, the activation of constitutive nitric oxide synthase releases nitric oxide, leading to vasodilation. However, in patients with atherosclerosis or cardiac risk factors, vasodilation is attenuated and this may be important in the pathogenesis disturbances in regional and coronary blood flow leading to coronary ischemia.¹¹ Although many other locally produced vasoactive substances including prostacyclin, endothelium-derived hyperpolarizing factor, endothelin, and thromboxane, are important in controlling vascular tone, nitric oxide plays a key role (Figure 7.1). This chapter will thus focus, on the role of endothelium-derived nitric oxide in the control of coronary conduit vessel vasomo-tion and coronary blood flow and the abnormalities in this system which are seen with atherosclerosis and related conditions.