Modulation of intrinsic cavernous tone and nitric oxide production by arginase in rabbit corpus cavernosum.
OBJECTIVE
Arginase shares the common substrate L-arginine with nitric oxide synthase (NOS). We investigated the roles of NOS and arginase for modulating intrinsic and vasoconstrictor tone in rabbit corpus cavernosum (RCC).


METHODS
Isolated RCC tissues were used for isometric tension experiments, and NOS and arginase activities. The endothelium lining RCC lacunar spaces was disrupted and/or removed by saponin treatment.


RESULTS
Following stretch of approximately 1gm NG-nitro-L-arginine methyl ester (L-NAME) as a NOS inhibitor caused endothelium dependent contraction, while the potent and specific arginase inhibitor N omega-hydroxy-nor-L-arginine (nor-NOHA) caused endothelium dependent relaxation. Relaxation with nor-NOHA was reversed by L-NAME. In the presence of 10 mM L-arginine 0.1 mM nor-NOHA was ineffective. Pretreatment with 0.1 mM L-NAME and 0.1 mM nor-NOHA did not significantly affect the vasoconstrictor response to phenylephrine. The magnitude of contraction with 0.1 mM L-NAME and relaxation with 0.1 mM nor-NOHA during contraction induced by phenylephrine were not significantly different from changes with L-NAME and nor-NOHA under intrinsic basal tone. In the enzymatic study NOS and arginase were detectable in cavernous homogenates. Nor-NOHA inhibited arginase but not NOS activity.


CONCLUSIONS
Results indicate that basal nitric oxide production from the endothelium regulates intrinsic cavernous tone and endogenous arginase activity in the endothelium modulates tone by inhibiting nitric oxide production, presumably through competition with constitutive NOS for the common substrate L-arginine.
Masuda
Hitoshi
H
Department of Urology, Institute of Biomaterials and Bioengineering, Graduate School, Tokyo Medical and Dental University, Japan.
Yano
Masataka
M
Sakai
Yasuyuki
Y
Kihara
Kazunori
K
Yamauchi
Yukinaao
Y
Azuma
Hiroshi
H
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010413:Penis / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits
D009569:Nitric Oxide; C068309:N(omega)-hydroxyarginine; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester