Vasomotor functions

Endothelial cells produce vasodilating and vasoconstricting substances that effect vascular smooth muscle. The main vasodilating substance produced, endothelial derived relaxing factor was detected in 1980 and identified as nitric oxide (NO) in 1987. Another vasodilator produced by endothelial cells is prostacyclin (Prostaglandin I2, PG-I2). The main vasocontrictors are endothelin-1, thromboxane-A2, superoxide anion and prostaglandin H2 (PG-H2), see figure 1.

There are receptors on the endothelial cell for acetylcholine, bradykinin, serotonin, thrombin and substance P. Activation of these receptors results in production and release of NO.

One of the characteristics of endothlial dysfunction is impairment or loss of endothleium-dependent vasodilatation. This is due to an imbalance between vasodilators and vasocontrictors with respect to production and release.

Figure 9: Schematic representation of endothelial derived smooth muscle relaxation. The endothelial cell is at the top of the diagram, the smooth muscle cell at the bottom and the basmement membrane inbetween. Various neurotransmitters, thrombin and substance P stimulate nitric oxide synthetase (cNOS). cNOS converts L-arginine to nitric oxide (NO). NO is released luminally and abluminally. On the abluminal side NO activates guanyl cyclase to increase the amount of cGMP in the smooth muscle cell. This results in relaxation. cNOS is constitutively expressed, expression may be enhanced by shear stress and estrogen. The activity of cNOS may be increased rapidly without increased expression by shear stress which probably activates a tyrosine kinase.