Impaired cavernous reinnervation after penile nerve injury in rats with features of the metabolic syndrome.
BACKGROUND
The metabolic syndrome is a cluster of cardiovascular risk factors that predispose toward the development of diseases such as diabetes. Erectile dysfunction (ED) is common in men with metabolic syndrome, but its etiology is poorly understood. Pro-erectile nitrergic nerves innervating penile erectile tissue are also susceptible to mechanical injury during pelvic surgical procedures, which can lead to sexual dysfunction.


OBJECTIVE
The aims of this article are: (i) to examine erectile function in an experimental model of metabolic syndrome, the phosphoenolpyruvate carboxykinase (PEPCK)-overexpressing rat; and (ii) to study function and cavernous reinnervation after penile nerve crush injury, which permits regeneration, in transgenic rats.


METHODS
We analyzed the density of noradrenergic and nitrergic nerves and performed organ bath pharmacology to assess neurogenic activity.


METHODS
By analyzing changes in neural structure, function, and pharmacologic responses of cavernous tissue after nerve crush injury, we were able to reveal neurologic deficits in rats with metabolic syndrome.


RESULTS
Animals with features of metabolic syndrome did not develop notable changes in cavernous autonomic nerve density or nerve-evoked smooth muscle activity. However, regeneration of nitrergic nerves after crush injury in transgenic rats was impaired compared with injured controls. This was manifested as a deficit in axon regrowth and responses to axon activation. However, unlike injured controls, injured PEPCK-overexpressing rats did not develop a reduced maximal response to the nitric oxide (NO) donor, sodium nitroprusside. This suggests preserved NO responsiveness in tissues from rats with metabolic syndrome, despite impaired regeneration and return of function.


CONCLUSIONS
This study revealed that rats with features of metabolic syndrome display impaired cavernous nerve regeneration after penile nerve injury, but the degree of functional impairment may be attenuated due to reduced plasticity of NO signaling. This reinnervation deficit may be of clinical relevance for understanding why ED persists in some (particularly aged) men after pelvic surgery.
Nangle
Matthew R
MR
Pain Management Research Institute and Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St. Leonards, New South Wales 2065, Australia. stish@med.usyd.edu.au
Proietto
Joseph
J
Keast
Janet R
JR
D000818:Animals; D017776:Autonomic Pathways / Q000503:physiopathology / Q000648:ultrastructure; D008297:Male; D024821:Metabolic Syndrome / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000502:physiology; D009416:Nerve Regeneration / Q000502:physiology; D010410:Penile Erection / Q000502:physiology; D010413:Penis / Q000294:innervation*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000378:metabolism; D051381:Rats; D055647:Rats, Transgenic / Q000502:physiology; D017208:Rats, Wistar
D019764:Phosphoenolpyruvate Carboxykinase (ATP)