37 - Nitric oxide and endothelin at the blood–brain barrier

Summary

Introduction

Endothelial cells play a key role in the local control of vascular tone, by releasing a variety of relaxing and contracting factors. The very labile ‘endothelium- derived relaxing factor’ first described by Furchgott and coworkers (Furchgott and Zawadzki, 1980) was later identified as nitric oxide (NO), the biological activity of which is now known to extend far beyond vasorelaxation, to host defence and neuromodulation. Together with several cyclooxygenase products (thromboxane A2, endoperoxides), endothelin largely contributes to endotheliumderived vasoconstricting activity. As with NO, it soon became obvious during the past decade that endothelin isopeptides (ET-1, -2, -3) are pleiotropic factors not only involved in vasoconstriction, but also in a number of physiological processes, such as cell proliferation or hormone secretion, and cardiovascular disorders, such as hypertension or stroke (Masaki and Yanagisawa, 1992). This chapter focuses on our current knowledge of the roles of NO and ETs in the control of cerebral circulation and cellular interactions at the level of the blood-brain barrier (BBB).

Nitric oxide

NO biosynthesis: cellular distribution and regulation

NO synthase isoforms NO is a small, relatively stable free-radical gas that diffuses through cell membranes and reacts with a number of cellular targets. It is synthesized by NO synthase (NOS) from L-arginine.