The successful long-term treatment of age related erectile dysfunction with hSlo cDNA in rats in vivo.
OBJECTIVE
We have previously reported that 1 intracorporeal injection of 100 microg hSlo/pcDNA reversed the effect of aging on erectile function in a rat model in vivo for at least 2 months. We report our further investigations of the amplitude, duration and physiological relevance of this novel gene transfer approach.


METHODS
A total of 191 retired breeder Sprague-Dawley rats were given a single intracavernous injection of phosphate buffered saline, 1,000 microg pcDNA, or 10, 100 or 1,000 microg pcDNA/hSlo. The animals were studied 1 to 6 months after injection. The intracorporeal pressure (ICP) response to cavernous nerve stimulation and immunostaining as well as hematoxylin and eosin staining were done to evaluate effector nerve integrity and tissue histology, respectively.


RESULTS
Gene transfer prevented an age related decrease in resting ICP and a physiologically relevant, significant effect on normalizing erection in vivo, as determined by submaximal (0.5 mA) and maximal (4.0 mA) cavernous nerve stimulation. The effects were observed 1 month after transfection and sustained for 6 months at the 100 and 1,000 microg doses of pcDNA/hSlo (p <0.026).


CONCLUSIONS
The physiological manifestations of gene transfer were detected as an amelioration of the age related decrease in resting ICP, and parallel increase in the magnitude of the cavernous nerve stimulated an ICP response to a level at which visible erections were again observed in this rat model of aging in vivo.
Melman
A
A
Department of Urology, Institute for Smooth Muscle Biology, Montefiore Medical Center, Albert Einstein College of Medicine, 3400 Bainbridge Avenue, Bronx, NY, USA.
Zhao
W
W
Davies
K P
KP
Bakal
R
R
Christ
G J
GJ
D000818:Animals; D007172:Erectile Dysfunction / Q000188:drug therapy* / Q000503:physiopathology; D015870:Gene Expression; D018014:Gene Transfer Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008297:Male; D010413:Penis / Q000473:pathology; D024681:Potassium Channels, Calcium-Activated / Q000627:therapeutic use*; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014661:Vasoconstriction / Q000502:physiology*
D051036:Large-Conductance Calcium-Activated Potassium Channels; D024681:Potassium Channels, Calcium-Activated