Differential alterations of prostacyclin, cyclic AMP and cyclic GMP formation in the corpus cavernosum of the diabetic rabbit.
OBJECTIVE
To investigate the effect of alloxan-induced diabetes mellitus (DM, a major risk factor for erectile dysfunction and associated with impaired endothelial function) on the formation of nitric oxide (NO), prostacyclin (PGI2), cGMP and cAMP in the corpus cavernosum of rabbits.


METHODS
Rabbits were rendered diabetic (hyperglycaemic, nonketotic) with alloxan; after 3 and 6 months, the penises were excised and the corpus cavernosum processed for the study of PGI2, NO, cAMP and cGMP formation, using a range of stimulators and radioimmunoassays.


RESULTS
PGI2 formation in response to acetylcholine and phorbol ester, but not arachidonate, and cGMP formation in response to A23187 (NO-release dependent), was significantly diminished in diabetic rabbit corpus cavernosum compared with controls at both 3 and 6 months after the induction of DM. cAMP formation in response to forskolin and prostaglandin E1 was reduced after 6 but not 3 months, although nitroprusside-stimulated cGMP (activates guanylyl cyclase directly) was unaffected in cavernosal tissue from diabetic rabbits.


CONCLUSIONS
These results show that the formation of NO and PGI2, and adenylyl cyclase activity but not guanylyl cyclase, are impaired in the corpus cavernosum of diabetic rabbits. As NO and PGI2 are produced by the endothelium, these studies consolidate the view that endothelial dysfunction is a major contributor to erectile dysfunction in diabetes mellitus.
Sullivan
M
M
Department of Urology, Royal Free Hospital and School of Medicine, London, UK.
Thompson
C S
CS
Mikhailidis
D P
DP
Morgan
R J
RJ
Angelini
G D
GD
Jeremy
J Y
JY
D000496:Alloxan; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D011464:Epoprostenol / Q000378:metabolism*; D007172:Erectile Dysfunction / Q000378:metabolism; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010413:Penis / Q000378:metabolism*; D011817:Rabbits
D009569:Nitric Oxide; D000496:Alloxan; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP