2.2. Physiology of penile erection

The central sensory psychogenic stimuli or penile stimulation or both increase parasympathetic activity, resulting in relaxation of the penile smooth muscle (Saenz de Tejada & Moncada 1996). This phenomenon is mediated by activation of the NO/cGMP pathway and by additional activation of the cAMP pathway, which result in increased blood flow through the penile arteries.

NO exerts a significant impact on the penis, operating as the princial mediator of ED (Burnett 1997). NO is a free radical and therefore a highly reactive and chemically unstable molecule. NO crosses the plasma membrane of cells targeting on the guanylate cyclase enzyme, producing a conformational change in the molecule that increases its activity. Activated guanylate cyclase catalyzes the conversion of guanosine-5``-triphosphate (GTP) to 3`,5`cyclic guanosine monophosphate (cGMP). The accumulation of cGMP sets in motion a cascade of events at the intracellular level which induce a loss of contractile tone of penile smooth muscle and increase of bood flow in cavernous body (Saenz de Tejada & Moncada 1996, Figure 2-1).

The other pathway for inducing relaxation and erection is mediated by vasoactive intestinal peptide (VIP) (Ehmke et al. 1995). The VIP receptors in the cavernous body are coupled to specific proteins that stimulate the catalytic activity of adenylate cyclase with the formation of cAMP (Figure 2-1). Endogenous prostanoids participate in the regulation of penile smooth muscle contractility. The receptor that mediates relaxation to PGE is designated ”EP receptor” (prostaglandin E receptor, Figure 2-1). The stimulation of beta-adrenergic receptors by catecholamines causes relaxation of the arterial and trabecular smooth muscle. The beta-2 subtype is probably the most important receptor mediating these effects (Dhabuwala et al. 1985). Adrenaline has high affinity for this receptor, whose stimulation partly counteracts the constrictor effects of this catecholamine, which are mediated by alpha-adrenergic receptors.

One of the mechanisms by which cyclic nucleotides induce the relaxation of smooth muscle is through the opening of potassium channels, which hyperpolarize the cell. The activation of potassium channels by PGE1 action, an effect mediated by AMPc, has been demonstrated (Christ et al. 1996).

The termination of erection takes place via increased adrenergic activity, and it has two components: a direct constrictor effect on the smooth muscle mediated by the alpha1- and alpha2-receptors and an indirect effect, whereby the vasodilatator effect of noncholinergic neurotransmitter nerves is inhibited by a prejunctional, alpha2-adrenergic-mediated mechanism (Saenz de Tajada & Moncada 1996).