Enhanced force generation by corpus cavernosum smooth muscle in rabbits with partial bladder outlet obstruction.
OBJECTIVE
Growing clinical evidence suggests that benign prostatic hyperplasia induced partial bladder outlet obstruction is associated with an increased incidence of erectile dysfunction. We determined whether corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction show any molecular or functional differences versus controls.


METHODS
Force generation and relaxation of corpus cavernosum smooth muscle 2 weeks after partial bladder outlet obstruction by 125 mM. KCl, phenylephrine and field stimulation were determined. Expression of total smooth muscle myosin and alternatively spliced smooth muscle myosin isoforms were determined by reverse transcriptase-polymerase chain reaction (RT-PCR), quantitative competitive RT-PCR, sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis. Corpus cavernosum smooth muscle from sections of the penis were analyzed morphologically by immunofluorescence microscopy using antibodies to smooth muscle myosin and neurofilament protein.


RESULTS
Corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction generated 40% to 50% more force than that of sham operated rabbits in response to KCl or phenylephrine and was more difficult to relax. Although quantitative competitive RT-PCR and sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that corpus cavernosum smooth muscle from rabbits with partial bladder outlet obstruction expressed only slightly more total smooth muscle myosin at the messenger RNA and protein levels, expression of the high adenosine triphosphatase isoform SM-B increased 2-fold. Morphological examination of corpus cavernosum smooth muscle sections revealed decreased innervation and increased smooth muscle bundle size.


CONCLUSIONS
We present the novel finding of molecular and functional changes in the corpus cavernosum smooth muscle associated with partial bladder outlet obstruction. Although the inclusion of sham operation ruled out direct injury during surgery, a change in corpus cavernosum smooth muscle innervation induced by nerve compression by the ligature is likely to induce trophic changes in the corpus cavernosum smooth muscle leading to over expression of the SM-B smooth muscle myosin isoform, increased contractility and impaired relaxation.
Chang
Shaohua
S
Division of Urology, Department of Pathobiology, University of Pennsylvania, Philadelphia, PA, USA.
Hypolite
Joseph A
JA
Zderic
Stephen A
SA
Wein
Alan J
AJ
Chacko
Samuel
S
DiSanto
Michael E
ME
D000818:Animals; D004591:Electrophoresis, Polyacrylamide Gel; D005455:Fluorescent Antibody Technique; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology*; D018995:Myosin Heavy Chains / Q000235:genetics / Q000378:metabolism; D018994:Myosin Light Chains / Q000378:metabolism; D010413:Penis / Q000294:innervation / Q000378:metabolism / Q000503:physiopathology*; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D011817:Rabbits; D020133:Reverse Transcriptase Polymerase Chain Reaction; D001748:Urinary Bladder Neck Obstruction / Q000378:metabolism / Q000503:physiopathology*
D018994:Myosin Light Chains; D020033:Protein Isoforms; D012333:RNA, Messenger; D010656:Phenylephrine; D011189:Potassium Chloride; D018995:Myosin Heavy Chains