Physiology Of Erectile Function And Dysfunction Part 2

The erectile tissue comprises multiple interconnecting sinusoidal spaces or lacunae surrounded by trabeculae of smooth muscle. During erection there is a considerable (up to eightfold) increase in the effective intrapenile blood volume, with corresponding expansion of the trabecular walls and lacunars spaces. Compression of the plexus of subtunical venides follows, reducing venous outflow. This phenomenon, often referred to as the venocclusive mechanism, produces an increase in penile volume (tumescence) and rigidity. Detumescence occurs through the reversal of this process fol’ lowing contraction of penile smooth muscle. The activation of sympathetic constrictor fibers causes an increase in the tone of the helicine arteries and the trabeculae. Arterial inflov is reduced and the lacunar space collapses.

Decompression of the subtunical venules follows, resulting in increased venous outflow. The penis is returned to the flaccid state. The overall tone of cavernosal smooth muscle represents an integrated response to many different pathways and systems, the details of which are incompletely understood. Peripherally, the local halance between contractant and relaxant factors controls the degree of contraction of the smooth muscle and determines the functional status of the penis. As elsewhere within the autonomic nervous system, sympathetic noradrenergic fibers and parasympathetic cholinergic fibers innervate the cavernosal tissue. In addition, there is innervation from nonadrenergic, noncholinergic (NANC) nerves. Within the NANC system a neuromodulator, nitric oxide, is released by nerve endings and endothelial cells, and acts postjunctionally to activate an intracellular enzyme cascade, culminating in erection.

Nitric oxide increases the production of cyclic guanosine monophosphate (cGMP) that decreases intracellular calcium, causing smooth muscle relaxation and penile engorgement. In turn, cGMP is broken down by phosphodiesterases (PDE5) . Inhibition of this enzyme forms the basis of the phosphodiesterase inhibitor story. The central nervous system (CNS) is fundamentally involved in the maintenance of normal erectile and sexual function as it initiates signaling to the penis via the autonomic nervous system and integrates the overall response. An action within the CNS could therefore represent an attractive option as a site of action of an erectogenic drug. Apomorphine SL was the first example of a centrally active drug approved for use in ED patients; other agents, with a range of target receptors, are being studied. Apomorphine is known to act on dopamine receptors in the brain. A signal is initiated that then travels within the autonomic nervous system to nerves in the pelvic area, dilating the cavernosal vasculature and causing an erection.