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Nitric oxide-mediated corpus cavernosal smooth muscle relaxation is impaired in ageing and diabetes
J J Cartledge1, I Eardley, J F Morrison
1Pyrah Department of Urology, St James's University Hospital, Leeds, UK. j.cartledge@ukgateway.net
Insights
Diabetes significantly impairs nitric oxide (NO)-mediated smooth muscle relaxation in rat penile tissue. This dysfunction is not due to superoxide anions but may involve cholesterol or advanced glycation end products.
Area of Science:
- Urology
- Physiology
- Endocrinology
Background:
- Diabetes mellitus is associated with erectile dysfunction.
- Nitric oxide (NO) mediates smooth muscle relaxation crucial for penile erection.
- Previous studies suggested impaired NO-mediated relaxation in diabetic cavernosal tissue due to superoxide anions.
Purpose of the Study:
- To investigate the impact of diabetes on NO-mediated relaxation in rat penile cavernosal smooth muscle.
- To determine the mechanisms underlying this impairment, specifically examining the roles of NO availability, superoxide anions, and constrictor prostanoids.
Main Methods:
- Diabetes was induced in male Wistar rats for 8 weeks.
- Cavernosal smooth muscle strips were contracted and then relaxed using acetylcholine, electrical field stimulation (EFS), or sodium nitroprusside (SNP).
- Relaxation responses were assessed in the presence of L-arginine, indomethacin, or superoxide dismutase (SOD).
Main Results:
- Diabetes significantly impaired relaxation responses to acetylcholine and EFS but not SNP.
- Neither L-arginine, indomethacin, nor SOD significantly reversed the diabetic impairment.
- Aging also caused a significant impairment in EFS-mediated relaxation.
Conclusions:
- Diabetes in rats leads to impaired endothelial and neuronal NO-mediated relaxation of penile smooth muscle in vitro.
- The impairment is not explained by altered intracellular NO action, NO availability, superoxide inactivation of NO, or constrictor prostanoids.
- Cholesterol or advanced glycation end products are potential contributors to diabetes-induced penile smooth muscle dysfunction.
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.
Materials And 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).
Conclusion:
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.
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