The effect of nitric oxide on the resting tone and the contractile behaviour of the external urethral sphincter: a functional urodynamic study in healthy humans.
OBJECTIVE
This functional urodynamic study assessed the effect of the nitric oxide donor isosorbide dinitrate on the external urethral sphincter and hypothesised first that nitric oxide could lower the resting sphincter pressure, second that nitric oxide could influence the sphincter contractility during magnetic stimulation, and third that nitric oxide could induce a faster external urethral sphincter fatigue during continuous magnetic stimulation.


METHODS
Eight healthy males gave their written informed consent and were included. A 2-channel microtip pressure transducer catheter was inserted into the urethra measuring the bladder and the external urethral sphincter pressure. Magnetic stimulation of the sacral roots was performed to evoke reproducible contractions of the external urethral sphincter. The baseline protocol included six single pulse stimulations and three stimulations 10sec in duration each for two frequencies 5Hz and 50Hz with intensities at the motor threshold of the pelvic floor. Then the subjects received 10 mg of isosorbide nitrate sublingually and the protocol was repeated 5min, 20min, 40min and 60min after drug administration.


RESULTS
The sublingual administration of isosorbide dinitrate could significantly reduce the resting pressure of the external urethral sphincter for at least one hour. The maximal contractile strength measured as the maximal urethral pressure during single pulse and continuous magnetic stimulation of the sacral roots also decreased significantly. Nitric oxide did not induce a significantly faster fatigue of the external urethral sphincter during continuous magnetic stimulation of the sacral roots.


CONCLUSIONS
This study shows a functionally relevant effect of nitric oxide on the resting tone and the contractile behaviour of the human external urethral sphincter in vivo while the fatigue properties did not changed significantly. Nitric oxide donors could offer a new pharmacological approach to treat urinary retention due to overactive or non-relaxing external urethral sphincter.
Reitz
André
A
Neuro-Urology, Swiss Paraplegic Center, Balgrist University Hospital, Forchstrasse 340, 8008 Zurich, Switzerland. areitz@balgrist.unizh.ch
Bretscher
Sibylle
S
Knapp
Peter A
PA
Müntener
Michael
M
Wefer
Björn
B
Schurch
Brigitte
B
D000328:Adult; D000704:Analysis of Variance; D004558:Electric Stimulation; D006801:Humans; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects* / Q000502:physiology; D009569:Nitric Oxide / Q000494:pharmacology*; D011312:Pressure; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D014563:Urodynamics / Q000187:drug effects* / Q000502:physiology
D009569:Nitric Oxide