Nitric oxide-dependent penile erection in mice lacking neuronal nitric oxide synthase.
BACKGROUND
Nitric oxide (NO) has been implicated as a mediator of penile erection, because the neuronal isoform of NO synthase (NOS) is localized to the penile innervation and NOS inhibitors selectively block erections. NO can also be formed by two other NOS isoforms derived from distinct genes, inducible NOS (iNOS) and endothelial NOS (eNOS). To clarify the source of NO in penile function, we have examined mice with targeted deletion of the nNOS gene (nNOS- mice).


METHODS
Mating behavior, electrophysiologically induced penile erection, isolated erectile tissue isometric tension, and eNOS localization by immunohistochemistry and Western blot were performed on nNOS- mice and wild-type controls.


RESULTS
Both intact animal penile erections and isolated erectile tissue function are maintained in nNOS mice, in agreement with demonstrated normal sexual behaviors, but is stereospecifically blocked by the NOS inhibitor, L-nitroarginine methyl ester (L-NAME). eNOS is abundantly present in endothelium of penile vasculature and sinusoidal endothelium within the corpora cavemosa, with levels that are significantly higher in nNOS- mice than in wild-type controls.


CONCLUSIONS
eNOS mediates NO-dependent penile erection in nNOS- animals and normal penile erection. These data clarify the role of nitric oxide in penile erection and may have implications for therapeutic agents with selective effects on NOS isoforms.
Burnett
A L
AL
Department of Urology, Johns Hopkins Hospital, Baltimore, Maryland, USA.
Nelson
R J
RJ
Calvin
D C
DC
Liu
J X
JX
Demas
G E
GE
Klein
S L
SL
Kriegsfeld
L J
LJ
Dawson
V L
VL
Dawson
T M
TM
Snyder
S H
SH
D000818:Animals; D003307:Copulation; D004542:Ejaculation; D004558:Electric Stimulation; D004790:Enzyme Induction; D005260:Female; D005298:Fertility; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000096:biosynthesis / Q000172:deficiency*; D007537:Isometric Contraction; D008098:Litter Size; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009130:Muscle, Smooth / Q000502:physiology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000096:biosynthesis / Q000172:deficiency*; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000294:innervation / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013237:Stereoisomerism
D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester