ABSTRACT
Based on the differential effects of inhibitors on endothelium-dependent responses induced by some, but not all agonists, De Mey et al. first suggested that certain endothelium-dependent vasodilators might release more than one endothelium-derived relaxing factor. Several later findings substantiated this hypothesis. In arterial tissues, muscarinic agonists hyperpolarize the cell membrane of the smooth muscle. The hyperpolarization is converted to depolarization after removal of the endothelium, suggesting that the latter generates an hyperpolarizing signal. In 1976, Moncada and Vane described that prostaglandin endoperoxides are transformed to prostacyclin by a microsomal enzyme from blood vessels into an unstable substance which has vasodilator properties and inhibits platelet aggregation. Prostacyclin is formed in vascular tissues of most mammalians, including humans, from arachidonic acid which is released from membrane phospholipids. Prostacyclin is the major product of cyclooxygenase in the blood vessel wall.
