Adenylate and guanylate cyclase activity in the penis and aorta of the diabetic rat: an in vitro study.
OBJECTIVE
To investigate the role of adenylate and guanylate cyclases in the mediation of erection in diabetic rats.


METHODS
Hyperglycaemic diabetes mellitus was induced in 35 rats using streptozotocin. Two months later the penises and aortae of these rats were excised and cut into rings or segments before being treated with varying concentrations of acetylcholine (Ach), sodium nitroprusside (NaNP), prostaglandin E1 (PGE1) and adrenaline (AD). The levels of adenosine 3'5'-cyclic monophosphate (cAMP) and guanosine 3'5'-cyclic monophosphate (cGMP) so generated were measured by radioimmunoassay and the results compared with those from seven age-matched control rats that had not been given streptozotocin.


RESULTS
Ach-stimulated cGMP synthesis was impaired in the aortae in diabetic rats. Ach-stimulated cGMP synthesis was undetectable in the penis. NaNP-stimulated cGMP and PGE1-stimulated cAMP synthesis was enhanced in both the penises and aortae in diabetic rats compared with controls. AD-stimulated cAMP synthesis was enhanced in the aorta in diabetic rats compared with controls, but AD had no effect on cAMP synthesis in the penis.


CONCLUSIONS
Ach-stimulated nitric oxide (NO) synthesis is impaired in the vasculature of diabetic rats and an Ach-NO axis may not be present in the penis of the rat. The enhanced capacity of the penis and vasculature to generate cAMP and cGMP may constitute an adaptive response to counteract the reduction in receptor-linked NO release. Impaired adenylate or guanylate cyclase activity does not contribute to erectile dysfunction in diabetic rats.
Miller
M A
MA
Department of Urology, Royal Free Hospital Trust and School of Medicine, London, UK.
Morgan
R J
RJ
Thompson
C S
CS
Mikhailidis
D P
DP
Jeremy
J Y
JY
D000262:Adenylyl Cyclases / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D006152:Cyclic GMP / Q000096:biosynthesis; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D006162:Guanylate Cyclase / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D010410:Penile Erection / Q000187:drug effects*; D010413:Penis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D009569:Nitric Oxide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D006162:Guanylate Cyclase; D006152:Cyclic GMP