Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes.
OBJECTIVE
To examine nitric-oxide (NO)-mediated relaxation in cavernosal smooth muscle in a rat model of diabetes, as previous experiments showed that HbA1c (an isoform of glycosylated haemoglobin and a marker of long-term diabetic control) impaired NO-mediated relaxation of normal corpus cavernosal tissue through the generation of superoxide anions.


METHODS
Eight weeks after the induction of diabetes, male Wistar rats were killed and cavernosal tissue obtained. Strips were contracted with 1 micromol/L noradrenaline before applying acetylcholine or electrical field stimulation (EFS) or sodium nitroprusside (SNP). Relaxation responses were repeated in the presence of L-arginine (100 micromol/L), indomethacin (10 micromol/L) or superoxide dismutase (SOD, 120 IU/mL). Young and age-matched control animals were examined in the same way.


RESULTS
Eight weeks of uncontrolled diabetes caused a significant impairment in mean relaxation responses to acetylcholine (P < 0.05) and to EFS (P < 0.05), but not to SNP, compared with young and age-matched controls, respectively. L-arginine, indomethacin and SOD had no significant effect on this impairment. Ageing caused a lesser but significant impairment in EFS-mediated cavernosal smooth muscle relaxation (P < 0.05).


CONCLUSIONS
Diabetes impairs endothelial and neuronal NO-mediated cavernosal smooth muscle relaxation in rats in vitro. This effect is not mediated by an alteration in the intracellular action of NO, the availability of NO, superoxide anion inactivation of NO or the generation of constrictor prostanoids. It is possible that cholesterol or advanced glycation end products are responsible for the effect of diabetes on penile smooth function.
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
D000109:Acetylcholine / Q000494:pharmacology; D000375:Aging / Q000502:physiology*; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D008297:Male; D009126:Muscle Relaxation / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D010413:Penis / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D009599:Nitroprusside; D009569:Nitric Oxide; D000109:Acetylcholine; D009638:Norepinephrine