elium-derived hyperpolarizing factor, acetylcholine, serotonin, histamine, and substance P.
             The endothelium also regulates vascular cell growth of smooth muscle cells. It does so by producing some of the platelet-derived growth factor that is also made by platelets and macrophages. This factor is released onto receptors of smooth muscle cells, causing proliferation and migration. Circulating macrophages may enter the endothelium and produce thrombin to convert fibrinogen into fibrin. The resulting thrombin-fibrin complex is a strong smooth muscle cell growth stimulus (Sheppard and Davies, 1998). There are also endothelial qualities that prevent smooth muscle cell growth. These are circulating nitric oxide, cyclic GMP, and L-arginine, a precursor of nitric oxide. The endothelium produces L-arginine, and this is converted by nitric oxide synthase into nitric oxide. The nitric oxide released into the lumen binds to cGMP, and concentration of cGMP increases, to inhibit smooth muscle cell proliferation.
             Endothelin and angiotensin II are the strongest vasoconstrictors. Angiotenin II acts directly by being actively transported through the epithelium and into the abluminal space, where it reacts with multiple smooth muscle cell receptors (Pepine et al, 1997). Endothelin is derived within the endothelium. Along with direct reaction onto a smooth muscle cell receptor, endothelin is feed-forward stimulated by angiotensin II. On the reverse side, endothelium houses nitric oxide, the powerful vasorelaxer. To function, nitric oxide production is stimulated by receptors on the endothelium responding to physical stimuli, such as shear stress, or physiologic stimuli such as bradykinin and acetylcholine. Nitric oxide travels into the smooth muscle cells, where it elevates the level of cyclic GMP, which relaxes the muscle. Also within the endothelium, nitr
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