Advanced glycation end-products are responsible for the impairment of corpus cavernosal smooth muscle relaxation seen in diabetes.
OBJECTIVE
To determine if advanced glycation end-products (AGEs) are responsible for the lower neuronal and endothelial-derived nitric oxide (NO)-mediated relaxation of corpus cavernosum in tissue in diabetic rats than in control rats.


METHODS
Diabetes was induced in male Wistar rats by an intraperitoneal injection with streptozotocin (60 mg/kg). One group of diabetic rats was given free access to water and standard diet. A second group was given standard diet and aminoguanidine with their water (50 mg/100 mL) from the initiation of diabetes. Two groups of rats that were not diabetic acted as age-matched controls. After 8 weeks animals were killed by cervical dislocation, corpus cavernosal tissue strips harvested and mounted in an organ bath to measure isometric tension. After 90 min of equilibration at optimal resting tension and contraction with 1 micromol/L noradrenaline, the response to either acetylcholine or electrical field stimulation (EFS) after adding guanethidine (5 micromol/L) and atropine (1 micromol/L) was determined for each group.


RESULTS
There was no difference between the baseline characteristics of all the experimental groups. After 8 weeks the mean body mass and glycosylated haemoglobin (HbA1c) were significantly greater in the diabetic than in control animals. Aminoguanidine had no effect on the recorded body mass or HbA1c. The in vitro relaxation response to the application of acetylcholine or EFS of tissue strips from age-matched control animals fed a standard diet and those supplemented with aminoguanidine were the same. The administration of aminoguanidine to diabetic animals for 8 weeks reversed the expected impaired relaxation response to acetylcholine; the response to EFS was similar.


CONCLUSIONS
AGEs are more prevalent in erectile tissue from diabetic than in control animals. Aminoguanidine reversed the impairment in neuronal and endothelial NO-mediated penile smooth muscle relaxation seen in diabetes. As aminoguanidine prevents AGE formation, erectile dysfunction in diabetes is probably caused partly by the generation of AGEs.
Cartledge
J J
JJ
Pyrah Department of Urology, St James's University Hospital, Leeds, UK. j.cartledge@ukgateway.net
Eardley
I
I
Morrison
J F
JF
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007172:Erectile Dysfunction / Q000503:physiopathology; D017127:Glycation End Products, Advanced / Q000502:physiology*; D006146:Guanidines / Q000494:pharmacology*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D010409:Penile Diseases / Q000503:physiopathology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D017127:Glycation End Products, Advanced; D006146:Guanidines; D009569:Nitric Oxide; C004479:pimagedine