Nitric oxide synthase gene therapy for erectile dysfunction: comparison of plasmid, adenovirus, and adenovirus-transduced myoblast vectors.
OBJECTIVE
Nitric oxide (NO) has been recognized as an important transmitter for genitourinary tract function. This transmitter mediates smooth muscle relaxation and is essential for erection. The objective of our research was to determine whether overexpression of nitric oxide synthase (NOS) in the corpus cavernosum of the penis would correct erectile dysfunction.


METHODS
We introduced the inducible form of the enzyme NOS (iNOS) into the corpus cavernosum of adult (250-300 g) male Sprague-Dawley rats by injecting a solution of plasmid, adenovirus, or adenovirus-transduced myoblast cells (adeno-myoblast) (N = 3-5 each group). We also injected plasmid, adenovirus, and adeno-myoblast encoding the expression of the beta-gatactosidase reporter gene.


RESULTS
We noted expression of beta-galactosidase throughout the corpora cavernosum after injection of each of the three solutions. Staining was greatest for adeno-myoblast followed by adenovirus and then plasmid. The basal intracavernous pressure (ICP) of iNOS-treated animals (adenovirus and adenovirus-transduced myoblast) increased to 55 +/- 23 cm H(2)O v 5 +/- 6 H(2)O in naive animals (P = 0.001). Stimulation of the cavernous nerve (15 Hz, 1.5 msec, 10-40 V, 1 min) resulted in a twofold increase in ICP (adenovirus and adeno-myoblast) from the basal level of the iNOS-treated animals. Direct in situ measurement of NO demonstrated release of 1 to 1.3 microM NO in the adeno-myoblast-treated penis.


CONCLUSIONS
Myoblast-mediated gene therapy was more successful in delivering iNOS into the corpus cavernosum than were the direct adenovirus or plasmid transfection methods. Gene therapy of NOS may open new avenues of treatment for erectile dysfunction. Control of NOS expression would be necessary to prevent priapism.
Tirney
S
S
Department of Urology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA.
Mattes
C E
CE
Yoshimura
N
N
Yokayama
T
T
Ozawa
H
H
Tzeng
E
E
Birder
L A
LA
Kanai
A J
AJ
Huard
J
J
de Groat
W C
WC
Chancellor
M B
MB
D000256:Adenoviridae; D000818:Animals; D002460:Cell Line; D007172:Erectile Dysfunction / Q000628:therapy*; D004926:Escherichia coli; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D008297:Male; D009569:Nitric Oxide / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000235:genetics*; D052247:Nitric Oxide Synthase Type II; D010413:Penis / Q000201:enzymology; D010957:Plasmids; D051381:Rats; D017207:Rats, Sprague-Dawley; D014162:Transfection; D001616:beta-Galactosidase / Q000032:analysis / Q000235:genetics
D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D001616:beta-Galactosidase