Reduced efficacy of nitrergic neurotransmission exacerbates erectile dysfunction after penile nerve injury despite axonal regeneration.
Penile (cavernous) nerves are readily damaged during radical prostatectomy, invariably causing impotence. Erectile function can return, however this may take months or years and capacity often remains poor. Many studies have attempted to improve penile nerve regeneration but have not explored mechanisms underlying the delay in functional recovery. This is assumed to be due to slow growth of axons, although penile tissues also change following loss of erectile activity. We have asked whether delayed recovery of the nitrergic nerve-evoked erectile response is due to pre-synaptic (slow axonal growth) or post-synaptic (changes in tissue responsiveness) mechanisms. These components were dissected in vitro following penile nerve injury in adult rats. Following crush of both penile nerves, excellent regeneration of nitrergic axons occurred after 10-12 weeks but neurogenic relaxation of cavernosum muscle was still relatively poor. This was at least partly due to attenuated tissue responsiveness to nitric oxide (using sodium nitroprusside as a donor) from 3 weeks after injury. Western blotting also revealed a modest reduction of soluble guanylyl cyclase. A second model of penile nerve injury, unilateral cut, completely denervated one side but retained potential for penile erection. Some anatomical and functional recovery occurred after 9-11 weeks (probably due to sprouting from contralateral uninjured axons), but nitroprusside-evoked relaxations were unaltered from at least 3 weeks onward. These data suggest that erectile dysfunction following extensive nerve injury may be exacerbated by postsynaptic changes in nitric oxide signaling, even when nerve regeneration occurs. This may be prevented by continued activation of penile tissues to retain normal perfusion.
Nangle
Matthew R
MR
Pain Management Research Institute, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St. Leonards, NSW 2065, Australia. stish@med.usyd.edu.au
Keast
Janet R
JR
D000818:Animals; D001369:Axons / Q000378:metabolism*; D019771:Axotomy; D003714:Denervation; D007172:Erectile Dysfunction / Q000209:etiology / Q000503:physiopathology*; D006162:Guanylate Cyclase / Q000378:metabolism; D008297:Male; D009130:Muscle, Smooth / Q000201:enzymology; D009409:Nerve Crush; D009416:Nerve Regeneration; D009420:Nervous System / Q000503:physiopathology; D009569:Nitric Oxide / Q000378:metabolism*; D010413:Penis / Q000294:innervation*; D051381:Rats; D017208:Rats, Wistar; D009435:Synaptic Transmission; D020196:Trauma, Nervous System / Q000150:complications* / Q000503:physiopathology
D009569:Nitric Oxide; D006162:Guanylate Cyclase