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

endothelium is the main chemical mediator of the vasodilatation
and trabecular relaxation involved in penile erection.

The catalytic production of NO requires the enzyme NO synthase,
expressed in many biological tissues as 3 main isoforms: two
constitutive isoforms, neuronal NOS (nNOS) and endothelial NOS
(eNOS), that require Ca2+ and calmodulin for activity, and one
inducible isoform (iNOS), that is Ca2+- and calmodulin- independent
and is expressed in response to inflammatory mediators (42). nNOS
and eNOS are the principal isoforms involved in penile erection and
are present in the nerves and endothelium of the penis, respectively
(43-45). nNOS is present in the pelvic plexus and in terminal
branches of the cavernous nerves innervating the trabecular smooth
muscle and penile vasculature (43, 46). nNOS and vesicular ACh
transporter (VAChT) are co-localized in most nerve terminals
surrounding penile small arteries which suggests that ACh and NO
coexist in the same parasympathetic cholinergic neurons that control
penile arterial tone (44, 45).

Investigations by our group first provided functional evidence for
the involvement of NO in the NANC inhibitory neurotransmission of
penile resistance arteries or helicine arteries. Thus, the NANC
relaxations elicited by electrical field simulation (EFS) were
endothelium-independent, inhibited by the L-arginine analogue, NG-
nitro-L-arginine, by the NO scavenger, oxyhaemoglobin, and by
inhibitors of guanylate cyclase (47, 48). Moreover, exogenous NO
and nitrosothiols mimicked the vasodilatation induced by EFS (22,
47, 48), which suggests that NO or a NO-like substance released
form nitrergic nerves mediates the neurogenic relaxations of penile
resistance arteries.

Until recently, the defined role of nNOS and eNOS in penile
erection has been a subject of debate, specially because erectile
function and mating behaviour are preserved in mice lacking the
genes for eNOS and nNOS (49, 50). Recently, a nNOS gene variant
resulting from alternative mRNA splicing of the ßnNOS in exon 1
has been confirmed as a major mediator in penile erection by using
nNOS, eNOS and doubly mutant deficient mice (51).

Concerning the role of other neural mediators released from
parsympathetic nerve terminals during penile erection, the classical

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