Paracrine function of endothelium-derived nitric oxide

We explored whether endothelium-derived nitric oxide (EDNO) acts in an autocrine or paracrine fashion to activate the soluble guanylate cyclase by measuring the elevations of cGMP levels. Comparisons were made between two culture models in which EDNO can stimulate cGMP synthesis within the same cells (endothelial cells) where it is formed, or in the neighboring cells (smooth muscle cells). The basal amount of EDNO showed no difference in cGMP levels when the endothelial cells (EC) were cultured either alone (iso-culture) or together with the smooth muscle cells (SMC, co-culture). However, cGMP levels were synergistically increased by the BK-stimulated EDNO when EC were co-cultured with SMC. The synergistical increase was significantly inhibited by 3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186), an extracellular radical scavenger. These findings suggest that the tonic formed basal EDNO has an autocrine effect on cGMP levels of EC themselves. In contrast, BK-stimulated phasic formed EDNO has not only an autocrine effect, but also a paracrine effect on cGMP levels of EC themselves and the adjacent SMC.