Mechanisms of erection

Mechanisms of erection

Intracavernosal smooth muscle tone is by far the most important determinant
of intracavernosal blood flow. Approximatelyhalf of the cavernosal volume is
composed of smooth muscle, with the remainder consisting of either lacunar
spaces orcollagen. Collagen fibers are largely responsible for the passive
mechanical properties of cavernosal tissue. In contrast, activecontraction
of cavernosal smooth muscle is dependent upon a number of factors, including the
level of agonists(neurotransmitters, hormones and endothelium-derived
factors), adequate expression of receptors, integrity of
transductionmechanisms, calcium homeostasis, interaction of contractile
proteins, and intimate intracellular communication betweensmooth muscle
cells (gap junctions).

Cavernosal smooth muscle cells contain abundant amounts of the contractile
proteins, actin and myosin. Followingphosphorylation of myosin by adenosine
triphosphate (ATP), attachments (crossbridges) form between the light chains
ofthese two proteins and these attachments provide the mechanism for
contractile tone of smooth muscle. The expenditure ofenergy for maintaining
this state of tone is almost zero, but there is an absolute requirement for a
high concentration ofcytoplasmic free calcium.

Adequate calcium homeostasis is, therefore, fundamental to the normal
regulation of smooth muscle tone. Three majormechanisms are involved:

(1) Influx of extracellular calcium through voltageregulated
channels;

(2) Activation of membrane-bound receptors which allow extracellular
calcium to enter through receptor-operated channels;

(3) Activation of signal pathways which allow intracellular release of
calcium from the sarcoplasmic reticulum.

Relaxation of cavernosal smooth muscle may be thought of as 'resetting' the
contractile machinery. This is mainlyaccomplished by lowering intracellular
calcium. There are a number of mechanisms by which this may be achieved but,
ingeneral, all pathways depend on either the accumulation of cyclic
adenosine monophosphate (cAMP) or cyclic guanosinemonophosphate (cGMP), or
the activation of potassium channels with consequent hyperpolarization of the
cellular membrane(Figure 16).

Nitric oxide, produced from its precursor L-arginine by nitric oxide synthase
(NOS), appears to exert two effects within thecorpora (Figure 17):

(1) Activation of potassium-channel ATPase, resulting in
hyperpolarization of the smooth muscle cell membrane. Thishyperpolarization
prevents the opening of voltage-dependent calcium channels, thereby reducing
intracellular calcium;

(2) Activation of guanylate cyclase which catalyzes the conversion of
guanosine triphosphate (GTP) to cGMP. This triggersrelaxation by lowering
intracellular calcium.

Other muscle relaxants act via cAMP-dependent mechanisms and include
prostaglandin (PG) E1 and vasoactive intestinalpolypeptide (VIP). These
substances react with membrane receptors coupled to a G protein which stimulates
adenylatecyclase to produce cAMP, thus lowering intracellular calcium. The
presence of two distinct and separate pathways to induceintracorporeal
vasodilatation is probably a reflection of the importance of the erectile
mechanism in the perpetuation of thespecies.

The breakdown of cGMP, accomplished mainly by phosphodiesterase type 5
(PDE5), raises cytoplasmic free calciumlevels and reverses smooth muscle
relaxation. Compounds such as papaverine and the recently discovered, more
selective,molecule sildenafil inhibit intracorporeal PDE5, thereby
increasing the intracellular half-life of cGMP and, thus, promotingand
prolonging smooth muscle relaxation and erection.