Full understanding of the PDE-5 inhibitors' mechanism of action requires a grasp of the salient features of erectile physiology. On sexual stimulation, nitric oxide (NO) is released from parasympathetic and nonadrenergic/noncholinergic nerve endings, and possibly from the endothelium of the blood vessels, in the penis. This in turn activates the enzyme called protein kinase G, the phosphorylation of other proteins, and the movement of calcium out of the cells.
That series of biochemical events relaxes the smooth muscles in the penile arteries and sinuses. The vessels' dilation enables blood to gush into the penis at high pressure, the sinuses' dilation occludes the penile veins by pushing them against the tunica albuginea, and the blood is trapped in the penis. The resulting erection is then made firmer by contraction of the muscles surrounding the penile shaft. Thus several pro-erectile substances play roles in producing and maintaining erection.
After a while, the antierectile enzyme PDE-5 spoils this happy event by breaking down cGMP into inactive GMP, leading to the gradual loss of the erection, despite NO's efforts to maintain it. During this struggle between pro- and antierectile substances is when the PDE-5 inhibitors intervene. These drugs block the action of PDE-5 on cGMP, thereby enhancing the smooth muscle relaxation of the arteries and sinuses and maintaining the erection. But remember that PDE-5 inhibitors do not have any effect on sexual desire, and they do not act in the absence of sexual stimulation.