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DOLORES PRIETO Y ALBINO GARCÍA SACRISTÁN ANAL. REAL ACAD. NAC. FARM.

NO is basally released from the arterial endothelium, as shown by
the increase in sponaneous myogenic tone after blockade of NOS in
human and equine penile small arteries (22, 48). The relative contri-
bution of endothelial NO to the agonist-induced vasodilations of the
erectile tissues is variable, being more relevant in CC and large penile
arteries and veins (23, 24, 48) than in the small penile resistance arte-
ries where a non-NO non-prostanoid factor is a major component of
the endothelium-dependent relaxant responses (22, 64, 65).

The physiological contribution of endothelial NO released by
shear-stres to penile vasodilatation has recently been suggested by
cllinical investigations demonstrating a flow-dependent arterial
dilatation, measured by the changes in the cavernous artery diameter
after 5 min occlusion of penile flow (66). These studies showed that
flow-induced vasodilatation is strongly impaired in patients with
organic ED and prosposed this measurement as a clinical test to
evaluate penile endothelial function. However, the involvement of
NO in the flow-dependent dilatation of penile arteries awaits further
confirmation, although recent studies have elucidated the link
between increased blood flow to the penis and eNOS activity, thus
also clarifying the physiological interaction between endothelial and
nerve-derived NO during penile erection. Thus, erection elicited by
cavernosal neve stimulation is mediated by phosphatidylinositol 3-
kinase (PI3-kinase) and activation of the protein kinase Akt. (67).
This pathway phosphorylates eNOS at Ser-1177 thereby increasing
endothelial-derived NO (68) and is responsible for sustained NO
production and the maintenance of maximal erection (67, 69). The
most important physiological agonist for such eNOS activation is
shear stress, although several hormones and growth factors also
increase the activity of PI3-K and endothelial NO production after
phosphorylation of eNOS. This pathway thus explains the role and
interactions nNOS and eNOS during penile erection. Neural NO–
mediated vasodilatation and increased blood flow to the CC produced
by parasympathetic activation during the initiation of erection leads
to shear-stress mediated stimulation of the endothelial lining in
penile arteries, which in turn releases NO from the endothelium and
produces further vasodilatation and sustained erection.

The subcellular location of eNOS, its interaction with the protein
caveolin-1 and the phophorylation state of serine and treonine

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