Relaxation vascular smooth muscle cells to form nitric oxide (NO). NO mediates smooth muscle relaxation by activating guanylate cyclase to increase intracellular concentrations of cGMP. cGMP activates protein kinases that can regulate free Ca2+ levels in the muscle cell and cause relaxation of smooth muscle by phosphorylating MLCK.
A short-lived free radical gas, NO is widely distributed in the body and plays an important role by its effect through cGMP on the smooth muscle vasculature. It is synthesized in the vascular endothelial cell from the semiessential amino acid l-arginine by NO synthase. After production in the cell, it diffuses to the smooth muscle cell, where it activates the enzyme guanylate cyclase, which leads to an increase in cGMP and then muscle relaxation (Fig. 19.3). Endothelium-derived relaxing factor (EDRF), released from the endothelial cell to mediate its smooth muscle-relaxing properties through cGMP, is identical with NO.
Inhibitors of phosphodiesterases of cAMP and cGMP also cause smooth muscle relaxation. These inhibitors increase cellular levels of cAMP and cGMP by preventing their hydrolysis to AMP and GMP, respectively. Drugs such as papaverine (see Chapter 17), theophylline (see chapter on
Nitrovasodilators Endothelial Cells
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