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

hyperpolarization of the adjacent smooth muscle cells by activating
K+ channels and/or the Na+-K+ ATPase (62, 70). In penile small

arteries, endothelial intermediate-conductance KCa channels have
been shown to be involved in the release of a non-NO non-prostanoid

factor in rat intracavernous arteries (71), although the identity of

EDHF remains to be clarified.

Intracellular signalling pathways underlying penile
vasodilatation

NO constitutively produced and released from nerve terminals
and endothelial cells diffuses into adjacent vascular or trabecular
smooth muscle cells and binds to the enzyme guanylate cyclase to
increase intracellular cGMP levels and the activity of the cGMP-
dependent protein kinase (PKG) (5, 6, 63). The essential role of the
PKG-mediated relaxation in the erectile process has been shown in
PKG-deficient mice that are unable to reproduce and have impaired
relaxations in response to neural- and endothelial-derived NO (72).

Both PKG and the cAMP-dependent kinase PKA can modulate
the activity of K+ channels thereby enhancing K+ efflux and reducing
[Ca2+]i to elicit vasodilatation (73,74). KCa channels are activated by
intracellular Ca2+ and depolarization and they are involved in the
maintenance of resting tone and are downstream mediators of the
NO/cGMP signalling cascade in both CC and penile resistance
arteries (7, 8, 22, 47, 75). Thus, the relaxations induced by NO and
NO donors in horse penile resistance arteries are inhibited by
charybdotoxin and iberiotoxin, and this inhibition is not further
increased by blockers of PKG thus suggesting that the relaxant effect
of NO is due in part to activation of large conductance KCa (BKCa)
through a PKG-dependent mechanism (22, 47, 75). In horse deep
dorsal penile veins, voltage-dependent K+ channels are involved in
the maintenance of basal tone and also in the cGMP-mediated NO-
induced vasodilatation (24).

The NO/cGMP signalling pathway underlying penile erection
involves several targets available for pharmacological intervention in
ED, the most prominent identified thus far being phosphodiesterase
5 (PDE5), the enzyme which enzymatically converts cGMP to its

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