Roles of attenuated neuronal nitric-oxide synthase protein expression and accelerated arginase activity in impairing neurogenic relaxation of corpus cavernosum in aged rabbits.
OBJECTIVE
To investigate whether changes in neuronal nitric oxide synthase (nNOS) protein expression and arginase activity are implicated in impairing the neurogenic cavernosal relaxation in aged rabbits, as NO is important in the neurogenic relaxation of corpus cavernosum during the erectile state.


METHODS
Cavernosal specimens of young adult (3-6 months old) and aged (36-48 months old) rabbits were used for isometric tension experiments, Western blot analysis, cGMP determination and measurements of NOS and arginase activities.


RESULTS
The neurogenic relaxation and cGMP production in response to electrical-field stimulation were significantly impaired in aged cavernosal specimens. Western blot analysis showed that nNOS protein was highly expressed in cavernosal specimens from young rabbits, but was undetectable or greatly decreased in old rabbits, with no change in overall NOS activity. Arginase activity in aged cavernosal specimens was significantly higher than in young rabbits. Supplementing with excess l-arginine, or giving S-(2-boronoethyl)-l-cysteine as an arginase inhibitor, significantly increased the neurogenic relaxation at lower frequencies only in the younger rabbits.


CONCLUSIONS
These results suggest that impairment of neurogenic and NO-mediated relaxation in the aged corpus cavernosum possibly results from the down-regulation of nNOS protein. The reduced l-arginine bioavailability to nNOS due to accelerated arginase activity would lead to further impairment of neurogenic NO production, in concert with decreased nNOS protein expression.
Numao
Noboru
N
Department of Urology, Tokyo Medical and Dental University, Yushima, Tokyo, Japan. noboru.uro@ymd.ac.jp
Masuda
Hitoshi
H
Sakai
Yasuyuki
Y
Okada
Youhei
Y
Kihara
Kazunori
K
Azuma
Hiroshi
H
D000375:Aging / Q000502:physiology*; D000818:Animals; D001119:Arginase / Q000378:metabolism*; D015153:Blotting, Western; D006152:Cyclic GMP / Q000378:metabolism; D007172:Erectile Dysfunction / Q000209:etiology*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000503:physiopathology; D052248:Nitric Oxide Synthase Type I / Q000378:metabolism*; D010410:Penile Erection / Q000502:physiology*; D011817:Rabbits
D052248:Nitric Oxide Synthase Type I; D001119:Arginase; D006152:Cyclic GMP