What are the key features of the structure of the endothelium? Give an account of the main actions of NO. Describe how NO is produced, and how secretion is regulated.

The Endothelium

The endothelium is constructed of a layer of oblong shaped cells, constituting a simple squamous epithelium, lining the lumen of all blood vessels. The endothelial cells are 0.2-0.3 micrometers thick and are cobblestoned in a single layer, with narrow clefts (intercellular clefts) between them. The cytoplasm of the endothelium notably includes a calcium store, the significance of which is related to NO production. The membrane is either fenestrated, in which it contains holes, or fenestrations within it, discontinuous, in which case it has certain breaks in coverage of around 100 nm, or continuous, where the membrane covers the lumen entirely.

NO (Nitric Oxide)

NO (Nitric Oxide) is a vasodilator which causes the expansion of the blood vessel, as well as an increase in the intercellular clefts. The vasodilation works by inhibiting the contraction of smooth muscle cells within the vessel, and further inhibits platelet aggregation and leukocyte binding.
? Vasodilation (ligand mediated [cNOS] and flow dependent [iNOS])
? Inhibition of vasoconstrictor influences (e.g., inhibits angiotensin II and sympathetic vasoconstriction)
? Inhibition of platelet adhesion to the vascular endothelium (anti-thrombotic)
? Inhibition of leukocyte adhesion to vascular endothelium (anti-inflammatory)
? Antiproliferative (e.g., inhibits smooth muscle hyperplasia following vascular injury)
? Scavenging superoxide anion (anti-inflammatory)

NO Control

NO is controlled by Nitric Oxide Synthase (NOS). NOS itself is produced by either constitutive or inductable NOS (cNOS or iNOS). cNOS reacts with high levels of calcium (calcium calmodulin) to form NOS, and hence the intercellular calcium channels can be opened to produce vasodilation by NO, or by means of the calcium that is released from subsarcolemmal storage sites in response to the binding of certain ligands to their receptors. iNOS is synthesised as a result of high shear stress. It is cytosolic and does not need the calcium calmodulin levels to engender production. The action of iNOS is more effective than cNOS, taking many hours, and producing up to 1000 times more NO.