Endogenous nitric oxide-mediated relaxation and nitrinergic innervation in the rabbit prostate: the changes with aging.
BACKGROUND
Nitric oxide (NO) plays the key role in the non-adrenergic non-cholinergic (NANC) nerve-mediated relaxation of prostate. We tried to determine whether nitrinergic innervation of the prostate is reduced with aging, and whether a reduction of this innervation alters the relaxant properties of prostatic tissue.


METHODS
The prostate isolated from young rabbits at the age of 3 months and aged rabbits at the age of 24 months was used. Pharmacologic experiments using electrical field stimulation (EFS) were performed on strips of prostate. Nitrinergic nerves were identified histochemically by the presence of NADPH diaphorase reactivity.


RESULTS
The prostate weighed 0.34 +/- 0.06 g in the young and 0.78 +/- 0.13 g in the aged (P < 0.01). Electrical stimulation caused frequency-dependent relaxation that was inhibited by N-nitro-L-arginine and increased by L-arginine. Maximum relaxant rates of noradrenaline-induced tone were 41.3 +/- 1.8% and 22.7 +/- 0.6% in the young and the aged (P < 0.01), respectively. Exogenous NO caused concentration-dependent relaxation of the prostate. Both relaxation induced by electrical stimulation and exogenous NO were inhibited by LY83583 (a guanylate cyclase inhibitor). In all specimens, NADPH diaphorase activity was observed in the smooth muscle layer of the prostatic stroma and capsule. However, NADPH diaphorase positive nerves were significantly less in the aged than in the young (P < 0.01).


CONCLUSIONS
As a result of these findings, it is suggested that both NO-mediated relaxation and nitrinergic innervation are reduced with aging in this animal model.
Aikawa
K
K
Department of Urology, Fukushima Medical University School of Medicine, Fukushima, Japan. kaika@fmu.ac.jp
Yokota
T
T
Okamura
H
H
Yamaguchi
O
O
D000375:Aging / Q000502:physiology*; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D001285:Atropine / Q000494:pharmacology; D004558:Electric Stimulation; D006145:Guanethidine / Q000494:pharmacology; D006651:Histocytochemistry; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009129:Muscle Tonus / Q000502:physiology*; D009130:Muscle, Smooth / Q000502:physiology*; D009252:NADPH Dehydrogenase / Q000378:metabolism; D009412:Nerve Fibers / Q000201:enzymology; D009569:Nitric Oxide / Q000502:physiology*; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology; D011467:Prostate / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology / Q000294:innervation*; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology; D014018:Tissue Distribution
D000634:Aminoquinolines; D009569:Nitric Oxide; D013779:Tetrodotoxin; D001285:Atropine; C041715:6-anilino-5,8-quinolinedione; D001120:Arginine; D011433:Propranolol; D009252:NADPH Dehydrogenase; D007213:Indomethacin; D006145:Guanethidine