Erections & Erectile Disorders
How Does the Penis Work?
Our improved understanding of penile physiology has led to better diagnosis and treatment of men with ED. We now recognize that two sets of processes are involved in penile function; one set maintains the flaccid condition, the other facilitates erection.
Factors that mediate naturally occurring erection
Erection occurs when nerve impulses from the brain (psychogenic erection) and from genital stimulation (reflexogenic erection) combine to cause blood to flow faster into than out of the penis. From this limited perspective, the penis can be viewed as a hydraulic organ. It is composed of three sponge-like cylindrical bodies that run the length of the penis (the two corpora cavernosa and the corpus spongiosum) which are supplied with blood by small branches of the penile artery. These helicine arteries empty into blood spaces (sinusoids) in this spongy tissue. The spaces are lined with vascular epithelial cells and are separated from each other by trabeculae, partitions made of smooth muscle. Blood is carried to the helicine arteries by branches of the pelvic artery and carried away from the sinusoidal spaces by surface veins than run adjacent to the sheath (tunica albuginea) that surrounds each corporal body.
The nervous input that induces erection is delivered to the penis via the pelvic nerve which exits the spinal cord at the lower sacral level (S2-S4) and branches into the cavernous nerve that supplies the corporal bodies. Both parasympathetic fibres that release acetylcholine (cholinergic fibres) and other nerves that release nitric oxide (NO) are involved in this process. It is damage to this nerve supply during some rectal and prostate surgeries that can cause post-treatment ED. Nervous input during sexual arousal causes dilation of the cavernosal arteries and results in a 30-40 fold increase in the rate of flow of blood through these arteries into the sinusoidal spaces. How does this nervous input cause the increased blood flow that initiates erection?
Nitric oxide (NO) and erection
When the penis is flaccid, the smooth muscle fibres that surround the sinusoids are contracted (thus restricting the rate of blood flow into the spaces of the corporal bodies. Erection occurs as a result of the action of NO on these smooth muscle fibres. NO activates the enzyme guanylate cyclase that converts guanosine triphosphate (GTP) to cyclic guanosine monophosphate (cGMP). cGMP causes smooth muscle relaxation (probably by decreasing cellular calcium which is needed for contraction) with a resulting increase in blood flow into the sinusoidal spaces. cGMP is inactivated naturally by an enzyme, phosphodiesterase type 5 (PDE-5), which is present in the smooth muscle cells. Sildenafil (Viagra TM) inhibits PDE-5 and thus prolongs the effect of cGMP in cases where its natural production is insufficient to cause or maintain an erection.
NO is released from the both the non-adrenergic non-cholinergic nerves (NANC) that supply the penis and also from the endothelial cells that line the sinusoids. The endothelial cells are triggered to release NO by acetylcholine from parasympathetic nerve fibres that are active during sexual stimulation. This explains why conditions that damage endothelial cells, such as high cholesterol, diabetes, or smoking, may also compromise erection. The mechanisms that mediate NO release and cGMP production and action are thus key features in the process of erection.
Although it is thought to play a lesser role than NO in facilitating erection, prostaglandin E1 (PGE-1) is also released from penile nerve endings during sexual arousal. Like NO, it activates production of a compound in smooth muscle cells that causes muscle relaxation. In this case, the compound is cyclic adenosine monophosphate (cAMP). PGE-1 activates the enzyme (adenyl cyclase) converts adenosine triphosphate (ATP) to cAMP). These observations explain why PGE-1 injected intercavernosally (Caverject TM) or inserted as a pellet intraurethrally (MUSE) can induce erection in men with ED. Other naturally occurring neuropeptides such as vasoactive intestinal peptide (VIP) may also be involved in the smooth muscle relaxation that leads to erection.
Restriction on venous outflow during erection
Continued filling of the sinusoids as a result of the above processes eventually compresses the veins that carry blood away from the penis against the tunica that surrounds the corporal bodies. This compression further facilitates erection by blocking blood outflow.
Factors that maintain the normal flaccid condition of the penis
In the flaccid penis, sympathetic nerve fibres release norepinephrine (such nerves are called noradrenergic) which binds to alpha 1 adrenergic receptors on penile smooth muscle to cause intracellular changes that result in contraction.
In some men damage to the endothelial cells may cause release of endothelin which can also cause smooth muscle contraction.
Our increasing knowledge of the physiological processes involved in erection makes it possible to understand the sites of action of the various medications currently being used or proposed to restore or enhance erectile function in men with ED.