Endothelial cells and other cell types

4.7.1 The endothelium - a large organ distributed throughout the body

Blood vessels are lined with a single layer of flat cells, endothelial cells: this lining is called the endothelium (Fig. 4.19). The whole endothelium in humans is large, weighing around 1.5 kg, with an area similar to that of a football pitch. Endothelial cells provide a smooth lining that reduces resistance to blood flow, but they are also very active in a number of ways. They regulate the contraction or relaxation of blood vessels (by sending signals to the muscle surrounding the

Fig. 4.19 The endothelium, a smooth single-celled lining of blood vessels.

Fig. 4.19 The endothelium, a smooth single-celled lining of blood vessels.

vessel), they provide a (regulatable) barrier to prevent cells and large molecules leaving the circulation and entering the surrounding tissue, and they also prevent blood clotting (unless there is damage to the vessel wall). We will consider the first of these functions since it is relevant to metabolism. It was recognised in 1980 that endothelial cells could produce a substance that caused blood vessels to dilate (by relaxation of the smooth muscle layer of the vessel). This substance was called endothelial-derived relaxing factor (EDRF). The discovery in 1987 that EDRF is the gas nitric oxide (NO) led to a Nobel Prize for three American pharmacologists, Robert Furchgott, Louis Ignarro and Ferid Murad (and also recognition of the part played by the British scientist Salvador Moncada whom many thought should have shared the prize). Now some people believe that hydrogen peroxide (H2O2) is also released by endothelial cells and has similar properties. NO is produced by the enzyme nitric oxide synthase, of which there are several isoforms. The one we are concerned with here is called endothe-lial NO-synthase, often abbreviated eNOS. NO is synthesised from arginine (Fig. 4.20). eNOS is activated by various stimuli, including stretching of the blood vessel: thus, if blood flow is tending to increase, for instance because the heart is pumping more blood, the vessels will respond (via NO production) by relaxing to allow the blood to flow freely. This is a mechanism for preventing undue increases in blood pressure. In some tissues, in particular skeletal muscle, eNOS is activated by insulin. Muscle blood flow will increase after a meal. Some people in the field believe (although this is controversial) that this assists in increasing glucose delivery to muscle cells so that glucose utilisation can increase following a meal.

Insulin or

Insulin or

Basement membrane

Relaxation ^ Js

Other effects

Smooth muscle layer

PKB cGMP

Guanylyl cyclase

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