Knowledge of the physiological processes underlying erection is essential in order to comprehend how the newest pharmacological agents exert their effects in treating male erectile disorder. Following is a brief summary of current understanding regarding the mechanism of erection.
Although various mechanisms of erection have been proposed, it appears certain that penile erection involves the preferential redirection of arterial inflow into the vascular spaces of the corpora cavernosa and that neurovascular mechanisms are involved. There is evidence of cholinergic and adrenergic innervation of corpora cavernosa, and dopaminergic neurotransmission may also be associated with the human erectile response. Other endogenous substances, such as nitric oxide, vasoactive intestinal polypeptide, and prostaglandins, have been reported to have a possible role in the mechanism of erection. There is also evidence that erection is regulated at both the spinal and the brain level (limbic and hypothalamic structures) and that the brain has both excitatory and inhibitory actions on the spinal mechanisms that control erection.
The regulation of human erection has several components, which are under the control of two pathways: 1) a mainly parasympathetic sacral one that mediates reflexogenic erections; and 2) a mainly sympathetic thoracolumbar one that mediates psychologically induced sexual stimulation (Schiavi 1999). In addition, input from sensory receptors in the penis is provided by the pudendal nerve. The initiating events of normal erection include tactile, visual, auditory, and imaginative stimuli that act centrally, primarily to increase parasympathetic outflow but also to inhibit sympathetic outflow; and local tactile stimuli that activate a penis-spinal cord-penis parasympathetic reflex arc. The main erectile mechanism is the relaxation of smooth muscles within the corpora cavernosa, which allows the inflow of blood to the penis.
The expansion of trabecular tissue against the wall of tunica albuginea shuts off the vein drainage. The increased blood inflow with decreased outflow leads to increased corporeal pressure and penile rigidity.
On the cellular level, activation of guanylate cyclase enzyme by nitric oxide leads to the conversion of guanosine triphosphate to cyclic guanosine monophosphate (cGMP). This process further leads to elevated intracellular second messenger concentrations and causes an efflux of intracellular calcium, thus leading to smooth-muscle relaxation. Nitric oxide is released from parasympathetic nerves and endothelial cells and also by the inhibition of alpha-adrenergic neurons in the arterial and trabecular smooth muscle during sexual stimulation. cGMP is metabolized by the phosphodiesterase 5 enzyme. It is important to note that testosterone has no effect on penile rigidity and is not therapeutically effective in eugonadal men with male erectile disorder.
Various substances, such as sildenafil, alprostadil, nitroglycerin, and others, could influence the relaxation of smooth muscles in corpora cavernosa through various mechanisms.
Revision date: June 14, 2011
Last revised: by Janet A. Staessen, MD, PhD