Nitric oxide synthase gene transfer for erectile dysfunction in a rat model.
OBJECTIVE
To determine whether over-expression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis improves erectile function, as NO is an important transmitter for genitourinary tract function, mediating smooth muscle relaxation and being essential for penile erection.


METHODS
The inducible form of the enzyme NOS (iNOS) was introduced into the corpus cavernosum of adult Sprague-Dawley rats (250-300 g) by injecting a solution of plasmid, adenovirus or adenovirus-transduced myoblast cells (adeno-myoblasts). Plasmid, adenovirus and adeno-myoblasts encoding the expression of the beta-galactosidase reporter gene were also injected into rats.


RESULTS
Throughout the corpora cavernosum there was expression of beta-galactosidase after injecting each of the three solutions. Maximum staining was greatest for adeno-myoblast, then adenovirus and then plasmid. The mean (sd) basal intracavernosal pressure (ICP) of iNOS-treated animals (adenovirus and adeno-myoblast) increased to 55 (23) cmH2O, compared with naive animals with a basal ICP of 5 (6) cmH2O (P = 0.001). Stimulating the cavernosal nerve (15 Hz, 1.5 ms, 10-40 V, 1 min) resulted in a doubling of the ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO showed the release of 1-1.3 micro mol/L in the adeno-myoblast penis.


CONCLUSIONS
Myoblast-mediated gene therapy was more successful for delivering iNOS into the corpus cavernosum than direct adenovirus injection or plasmid transfection. Surprisingly, implanting muscle cells into the penis is not only feasible but also beneficial. Gene therapy for NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.
Chancellor
M B
MB
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. chancellormb@msx.upmc.edu
Tirney
S
S
Mattes
C E
CE
Tzeng
E
E
Birder
L A
LA
Kanai
A J
AJ
de Groat
W C
WC
Huard
J
J
Yoshimura
N
N
D000256:Adenoviridae; D000818:Animals; D007172:Erectile Dysfunction / Q000628:therapy*; D018014:Gene Transfer Techniques; D008297:Male; D019001:Nitric Oxide Synthase / Q000008:administration & dosage* / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D010413:Penis / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001616:beta-Galactosidase