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DOLORES PRIETO Y ALBINO GARCÍA SACRISTÁN ANAL. REAL ACAD. NAC. FARM.
basal-released relaxant prostanoids (22). On the other hand, agonist-
induced endothelial stimulation of both human and rabbit CC and
horse deep dorsal penile veins evokes the release of contractile
prostanoids (23, 24). The main receptor involved in the contractile
effect of prostanoids in the human penis belongs to the PGH2/TP
type (25, 26).
Angiotensin II (AII) is locally formed in the endothelium and
smooth muscle of the CC, where its contractile effects are mediated
by muscular AT-1 receptors (27-29). Since AII levels are increased in
the cavernous blood during detumescence (29), this peptide has been
suggested to be involved in the initiation of detumescence as a
consequence of enhanced sympathetic activity. However, the
functional role of AII in penile arteries and veins remains to be
established.
Endothelins (ETs) are potent vasoconstrictor peptides synthesized
by endothelial cells that induce both contraction and ETB-mediated
relaxation of erectile tissues (30, 31). ETA and ETB receptors subtypes
are located at penile smooth muscle and nerves, respectively (30),
and infusion of ET-1 and ET-3 in the rat increases intracavernosal
pressure at low doses, and produces vasoconstriction followed by
decrease in pressure at high concentrations (32).
Intracellular mechanisms of penile vasoconstriction
Although elevation of [Ca2+]i is considered as a classical trigger
for force development, smooth muscle contraction can also be
modulated through inhibition of myosin light chain (MLC)
phosphatase (MLCP) by Ca2+-independent mechanisms resulting in
an increased MLC phosphorylation and force at constant [Ca2+]i,
which is referred to as Ca2+ sensitization (33). Vasoconstrictor agonists
binding G-protein-coupled receptors can stimulate both Ca2+
mobilization from intracellular stores and Ca2+ entry through both
dihydropyridine-sensitive L-type and non L-type Ca2+ channels (34).
Whereas in rat and human CC, there is a significant contribution
of Ca2+ from intracellular stores to phenylephrine-induced con-
tractions (35), in penile small arteries, a1-adrenoceptor- and TP
receptor-mediated contractions are largely dependent on Ca2+ entry
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