Fibrosis and loss of smooth muscle in the corpora cavernosa precede corporal veno-occlusive dysfunction (CVOD) induced by experimental cavernosal nerve damage in the rat.
BACKGROUND
Corporal veno-occlusive dysfunction (CVOD), which usually is associated with a loss of smooth muscle cells (SMC) and an increase in fibrosis within the corpora cavernosa, can be induced by an injury to the cavernosal nerves. The corporal tissue expresses inducible nitric oxide synthase (iNOS), presumably as an antifibrotic and SMC-protective response.


OBJECTIVE
We studied the temporal relationship in the corpora between the expression of iNOS, other histological and biochemical changes, and the development of CVOD, after bilateral cavernosal nerve resection (BCNR) in the rat.


METHODS
Rats underwent either BCNR or sham operation. Cavernosometry was performed 1, 3, 7, 15, 30, and 45 days (N = 8/groups) after surgery. Penile tissue sections were subjected to Masson trichrome staining for SMC and collagen, and immunodetection for alpha smooth muscle actin, iNOS, neuronal NOS (nNOS), endothelial NOS (eNOS), proliferating cell nuclear antigen (PCNA), and terminal transferase dUTP nick end labeling (TUNEL). Quantitative western blot analysis was done in homogenates.


METHODS
Time course on the development of fibrosis and CVOD.


RESULTS
Following BCNR, CVOD was detectable 30 days later, and it became more pronounced by 45 days. In contrast, the SMC/collagen ratio in the BCNR corpora was reduced at 7 days and bottomed at 30 and 45 days, due in part to the reduction of SMC, presumably caused by an increase in apoptosis peaking at 3 days. PCNA also peaked at 3 days, but then decayed. nNOS was reduced early (3-7 days) and disappeared at 30 days, whereas eNOS was not affected. iNOS was induced at day 3, and steadily increased peaking at 30 days.


CONCLUSIONS
CVOD develops in the BCNR rat as a result of the early loss of corporal SMC by the neuropraxia-induced apoptosis, which the initial cell replication response cannot counteract, followed by fibrosis. The time course of iNOS induction supports the antifibrotic role of iNOS.
Ferrini
Monica G
MG
Charles Drew University, Department of Medicine, Los Angeles, CA 90059, USA. monicaferrini@cdrewu.edu
Kovanecz
Istvan
I
Sanchez
Sandra
S
Umeh
Chiome
C
Rajfer
Jacob
J
Gonzalez-Cadavid
Nestor F
NF
D000199:Actins / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D004727:Endothelium / Q000378:metabolism; D005355:Fibrosis / Q000473:pathology*; D020287:In Situ Nick-End Labeling; D008297:Male; D009130:Muscle, Smooth / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000294:innervation / Q000473:pathology / Q000503:physiopathology; D010525:Peripheral Nerves / Q000473:pathology* / Q000503:physiopathology*; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley
D000199:Actins; D018809:Proliferating Cell Nuclear Antigen; D019001:Nitric Oxide Synthase