The interaction of homocysteine and copper markedly inhibits the relaxation of rabbit corpus cavernosum: new risk factors for angiopathic erectile dysfunction?
OBJECTIVE
To explore whether homocysteine (HCy), an independent risk factor for atherosclerosis (the angiopathic effect of which occurs through the generation of superoxide anions and hydrogen peroxide, augmented by copper, the superoxide anions reacting with nitric oxide, NO, to produce peroxynitrite, a highly angiopathic free radical) and copper contribute to erectile dysfunction (ED) through similar mechanisms, by assessing their interactive effects on the relaxation of corpus cavernosum using organ-bath techniques.


METHODS
Cavernosal smooth muscle strips were obtained from adult New Zealand White rabbits and mounted in organ baths. After precontraction with phenylephrine (100 micromol/L), relaxation responses to carbachol or sodium nitroprusside (SNP) were assessed in the presence or absence of HCy and copper. The effects of HCy and copper in the presence of superoxide dismutase or catalase were also investigated.


RESULTS
HCy alone inhibited carbachol-stimulated (NO-dependent) but not SNP-stimulated relaxations (NO-independent). This effect of HCy was significantly augmented by copper, which alone had no effect. The combined effect of HCy and copper was significantly (P<0.05) reversed by superoxide dismutase or catalase.


CONCLUSIONS
HCy inhibited NO-mediated cavernosal smooth muscle relaxation, an effect that was potentiated by copper and reversed by superoxide dismutase or catalase. It is therefore proposed that the effect of HCy on cavernosal smooth muscle relaxation is mediated by an interaction between NO and superoxide anions. Moreover, HCy may constitute a new risk factor for angiopathic ED.
Khan
M A
MA
Department of Urology, Royal Free and University College Medical School (University College London), Royal Free Campus & The Royal Free Hampstead NHS Trust, London, UK.
Thompson
C S
CS
Emsley
A M
AM
Mumtaz
F H
FH
Mikhailidis
D P
DP
Angelini
G D
GD
Morgan
R J
RJ
Jeremy
J Y
JY
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D003300:Copper / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006710:Homocysteine / Q000494:pharmacology*; D018783:Impotence, Vasculogenic / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010413:Penis / Q000187:drug effects*; D011817:Rabbits; D012307:Risk Factors
D006710:Homocysteine; D009599:Nitroprusside; D003300:Copper; D002217:Carbachol