Vasoactive substances such as Endothelium Derived Relaxing Factors (EDRF). Prostacyclin and Endothelin can be formed in the vascular endothelium. Endothelial dysfunction can lead to disturbances in coronary blood flow, contribute to the pathogenesis of myocardial ischaemia and is a central feature in the evolution of atherosclerosis, thrombosis, inflammation and atherogenesis (EDRF).

Intact endothelium is a prerequisite for acetylcholine-induced vasodilation. In the presence of endothelium, acetylcholine produces dose dependent vasodilation. When the endothelium is removed, only constriction is induced by acetylcholine. EDRF has been identified to be NO radical, or a sulfhydryl complex containing it. Only a few vasodilators can act independently of the endothelium and directly on vascular smooth muscle. These include the nitrovasodilators (e.g. Nitroglycerin, nitroprusside), prostacyclin and adenosine.

In patients with dysfunctional endothelium, the loss of flow mediated and catecholamine stimulated EDRF release allows the constrictor effects of the catecholamines to act unopposed. In vessels damaged by the atherosclerotic process and by plaque fissuring there is coronary constriction in response to a variety of substances that would normally elicit vasodilation.