Page 163 - 73_04

VOL. 73 (4), 963-985, 2007 PHISIOLOGY OF PENILE VASCULATURE...

This probably underlies arteriogenic ED induced by atherosclerosis
and other arterial occlusive diseases.

Local factors regulating penile vasodilatation

Relaxant prostanoids synthesized by both smooth muscle and
endothelial cells, are involved in the maintenance of penile arteriolar
tone (22, 26) and in the endothelium-dependent vasodilatations of
penile arteries in some animal species (54). Since PGE1 is the most
efficacious drug used in the intracavernous therapy of ED, its relaxant
effects are well characterized in both arterial and trabecular smooth
muscle of the penis. Thus, PGE1 evokes endothelium- and NO-
independent relaxations mediated by cAMP in horse penile resistance
arteries (59, 60), this relaxant effect of PGE1 in human arteries being
correlated with its clinical effectiveness when injected intracaver-
nously in patients (61). The vasodilator effects of PGI2 and PGE1 are
mediated by IP and EP (EP2/EP4) receptors coupled to Gs proteins and
to the activation of adenylate cyclase, in human penile arteries (26).

Role of the endothelium in the regulation of penile
vasculature

The endothelium, located at the interphase between blood and
the vascular wall, regulates the underlying vascular smooth muscle
tone by synthesizing short life vasoactive mediators such as NO,
endothelium-derived hyperpolarizing factor (EDHF), prostacyclin
(PGI2), AII and endothelins (ETs) (62).

Endothelial-derived NO is produced in the penis by activation of
eNOS in response to both hemodynamic stimuli like shear stress and
pulsatile stretch generated by increased blood flow, and by
neurohumoral factors such as ACh, bradikynin and histamine acting
on specific endothelial receptors (7, 8, 22, 24, 52). Activation of
eNOS by agonists is induced by increases in intracellular Ca2+
resulting from activation of G-protein-coupled receptors. Ca2+ binds
to calmodulin and this classic mode of eNOS activation by Ca2+/
calmodulin accounts for rapid and transient production of
endothelial NO (63).

973