Blood vessel and smooth muscle relaxation are controlled by cholinergic (with acetylcholine as a neurotransmitter from parasympathetic nerves) and nonadrenergic-noncholinergic fibers. Norepinephrine is the neurotransmitter. Adrenergic nerves constrict penile blood vessel and corpora cavernosum smooth muscle via alpah-1 adrenoreceptors. The pressure inside the corpus cavernosum is equal to the average arterial pressure, about 100 mm of Hg.

The venous occlusion mechanism is in full force with no venous drainage. The penis is rigid. The arterial inflow is now minimal. In this phase the trabecular smooth muscle is fully relaxed and the corpus cavernosum is full with newly infused arterial blood. As the overall pressure builds up inside the erectile cylinders, the arterial inflow begins to diminish. In this phase the volume of blood progressively increases and the pressure begins to increase inside each corpus cavernosum. Erection occurs. During erection, the parasympathetic nerves send the neurotransmitter Nitric Oxide (NO), which relaxes the trabecular smooth tissue, allowing it to stretch, which allows more blood inflow and simultaneously clamps off the veins which take blood out of the penis. Normally, sympathetic nerves are sending the neurotransmitter norepinephrine to the trabecular smooth muscle tissue, which is contracted.

As we will see in a later chapter, it functions to block PDE 5. Enter Cialis! It also is apparently located just in human penile tissue. Several other forms of phophodiesterase (PDE) have been identified in penile tissue (types 2, 3, 4 and 5); however, PDE 5 is the predominant phosphodiesterase in human corpus cavernosum and human corpus cavernosa smooth muscle.

The overall amount of intracellular cGMP, "man's favorite second messenger," is controlled by and regulated by the activity of the phosphodiesterase 5 (the villain to some), which helps convert cGMP back to GMP. This intracellular second messenger then carries out the final step in relaxing smooth muscle, reducing the level of intracellular calcium, by binding to cGMP - dependent protein kinases, cGMP dependent ion channels, and cGMP - regulated phosphodiesterases. This causes an increase in guanylyl cyclase activity, resulting in cyclic GMP (cGMP) production or synthesis. Once NO diffuses into the smooth muscle cell, it binds to an enzyme guanylyl cyclase . NO production (synthesis) results from activation of neurogenic and to a small degree, endothelial NO synthase. We now see that the NANC neurotransmitter nitric oxide (NO) is critical in producing smooth muscle relaxation and penile erection. Second-messenger molecules like cGMP function at the molecular level inside the cell in which they reside, in this case the smooth muscle of the corpora cavernosum . Vasodilation of the penile vascular structures, from primarily cavernous smooth muscle relaxation, following activation of cholinergic and NANC fibers is mediated by nitric oxide and its second messenger cyclic guanosin monophosphate (cGMP). Some of the NANC fibers may contain vasoactive intestinal polypeptide.