[Endothelial NO synthase].

Abstract

Nitric oxide (NO) may be produced in the vascular wall by different NO synthases. One of the constitutive isoforms, the endothelial NO synthase, contributes to the regulation of vascular tone and may prevent unwanted platelet and leucocyte adhesion to the endothelial surface. The release of NO by the endothelial NO synthase is exquisitely regulated by increases of intracellular free calcium following endothelial receptors activation by shear stress, neuromediators, hormones or platelet products. The immediate and transient release of NO diffuses towards the underlying smooth muscle and contributes to the appropriate response to local changes in blood flow or composition. The endothelial release of NO depends also on the availability of NO synthase cofactors; in addition, several experimental evidences suggest a transcriptional and postranscriptional regulation of the endothelial NO synthase itself. Another isoform of NO synthase insensitive to changes in intracellular calcium may be induced following exposure to cytokines or under some pathological conditions such as sepsis, inflammation or after vessel wall injury. The massive and long-lasting release of NO caused by induction of NO synthase requires a latency period of several hours. The inducible NO synthase may compensate the dysfunction of the endothelial isoform after injury (angioplasty) or in atherosclerosis. However, uncontrolled regulation of inducible NO synthase expression may have deleterious consequences on the vascular wall.