Localization of nitric oxide synthase activity in the human lower urinary tract and its correlation with neuroeffector responses.
OBJECTIVE
The present study was designed to correlate the localization of nitric oxide synthase (NOS) activity to nerve-induced smooth muscle responses in the human lower urinary tract.


METHODS
Nerve-induced smooth muscle activity was studied in the human lower urogenital tract. NOS activity was studied by measurement of citrulline formation and guanylate cyclase activity.


RESULTS
Nerve-induced contractions in the human detrusor muscle, bladder neck, and prostatic urethra were not significantly enhanced by the NOS inhibitor N omega-nitro-L-arginine methyl ester (L-NAME). In the prostatic urethra, relaxations to transmural nerve stimulation were obtained after increase in tension. The relaxations were abolished by L-NAME and restored by L-arginine. Nerve-induced relaxations were occasionally obtained in the bladder neck, whereas nerve-induced relaxations were never obtained in the detrusor muscle. Citrulline formation was highest in the prostatic urethra, it was intermediate in the bladder neck, and it was less pronounced in the detrusor muscle. Guanylate cyclase activity was also highest in the prostatic urethra, whereas there was no significant difference in guanylate cyclase activity in the bladder neck and detrusor muscle.


CONCLUSIONS
The nerve-induced smooth muscle responses and the localization of NOS activity were in good agreement. Thus, in areas where marked relaxations to nerve stimulation were obtained, there was also a high NOS activity. The data suggest that nitric oxide is a mediator for the neurogenic dilation of the bladder neck and urethra during the micturition reflex.
Ehrén
I
I
Department of Urology, Karolinska Hospital, Stockholm, Sweden.
Iversen
H
H
Jansson
O
O
Adolfsson
J
J
Wiklund
N P
NP
D000594:Amino Acid Oxidoreductases / Q000378:metabolism*; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D002956:Citrulline / Q000096:biosynthesis; D004558:Electric Stimulation; D006162:Guanylate Cyclase / Q000378:metabolism; D006801:Humans; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009252:NADPH Dehydrogenase / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester; D009469:Neuromuscular Junction / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D019001:Nitric Oxide Synthase; D014521:Urethra / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology
D002956:Citrulline; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases; D009252:NADPH Dehydrogenase; D006162:Guanylate Cyclase; D019331:NG-Nitroarginine Methyl Ester