New insights into the role of endothelin-1 in radiation-associated impotence.
The objectives of this work were to: (1) Determine if prostate and penile tissue levels of endothelin-1 (ET-1) are increased in a rat following pelvic irradiation. (2) Determine if an ETa receptor antagonist (BQ-123) potentiates erectile function in these irradiated animals. Rats were divided into three study groups: control, 1000 cGy and 2000 cGy. The experimental groups received a single dose of radiation to the pelvic region. A time course was established to measure the effects of irradiation on prostate and penile tissue levels of endothelin-1 (ET-1)-like immunoreactivity. The effect of intracavernous injection of BQ-123 (25 microg/30 microl) was evaluated by measuring intracavernous pressure (ICP) following cavernous nerve electrical field stimulation. In the 2000 cGy group, a significant rise in ET-1-like immunoreactivity tissue levels was observed at 20 days. A significant decrease in ICP was recorded in the 1000 and 2000 cGy irradiated rats compared to the control group. Only the 2000 cGy group had a significant improvement in erectile function following BQ-123 administration. A significant improvement was observed 20 min post-administration, lasted 90 min, and was back to pre-administered levels at 120 min. The conclusion made was that radiation-induced impotence in irradiated rats is associated with an increased production of ET-1. Preliminary results are suggestive that ETa receptor antagonist may be of use to reverse such radiation-induced impotence in these irradiated animals.
Merlin
S L
SL
Division of Urology, Department of Surgery, McGill University, Montreal, Québec, Canada.
Brock
G B
GB
Begin
L R
LR
Hiou Tim
F F
FF
Macramalla
A N
AN
Seyam
R M
RM
Shenouda
G
G
Dion
S B
SB
D000818:Animals; D004558:Electric Stimulation; D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1 / Q000502:physiology*; D007172:Erectile Dysfunction / Q000209:etiology* / Q000503:physiopathology*; D007267:Injections; D008297:Male; D010388:Pelvis / Q000000981:diagnostic imaging; D010410:Penile Erection / Q000187:drug effects; D010413:Penis / Q000473:pathology / Q000503:physiopathology; D010456:Peptides, Cyclic / Q000494:pharmacology; D011312:Pressure; D011467:Prostate / Q000473:pathology; D011832:Radiation Injuries / Q000150:complications*; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D013997:Time Factors
D065128:Endothelin Receptor Antagonists; D019332:Endothelin-1; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)