Altered nitric oxide synthase, arginase and ornithine decarboxylase activities, and polyamine synthesis in response to ischemia of the rabbit detrusor.
OBJECTIVE
Little is known about L-arginine catabolism following ischemia in the bladder. We examined the changes in nitric oxide synthase, arginase and ornithine decarboxylase activity, polyamine biosynthesis and the ability to produce nitric oxide following ischemia of the rabbit bladder.


METHODS
Bladder ischemia was created by ligation of a unilateral bladder artery. At various time points, that is 1, 4, 8, 24, 48 and 72 hours following ligation, the bladders were excised and harvested for determinations.


RESULTS
Constitutive nitric oxide synthase, inducible nitric oxide synthase arginase and ornithine decarboxylase activities increased with time, peaking at 48 hours without significant differences between the ligated and nonligated sides in the whole layer. Arginase and ornithine decarboxylase increased mainly in the muscularis following ischemia. Also, putrescine in the muscularis was significantly higher than in the mucosa 48 hours following ischemia. Baseline nitrite/nitrate production in the whole detrusor on the ligated side at 24 hours was significantly lower than that in the normal detrusor. However, nor-hydroxyarginine as an arginase inhibitor and L-arginine increased nitrite/nitrate production in the ischemic detrusor without changing in the normal detrusor. This increasing effect of nor-hydroxyarginine was abolished by nitroarginine methylester as a nitric oxide synthase inhibitor.


CONCLUSIONS
Enzymes related to L-arginine catabolism were involved in the early events of ischemic bladder. Arginase may have 2 independent roles, that is 1) activation of arginase/ornithine decarboxylase/polyamines pathways in the muscle injury and remodeling following ischemia, and 2) endogenous negative regulation of nitric oxide production by limiting the L-arginine substrate for nitric oxide synthase.
Kawano
Keizo
K
Departments of Urology and Reproductive Medicine and Biosystem Regulation, Institute of Biomaterials and Bioengineering, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bynkyo ward, Tokyo 113-8519, Japan. keizo.uro@tmd.ac.jp
Masuda
Hitoshi
H
Yano
Masataka
M
Kihara
Kazunori
K
Sugimoto
Akiko
A
Azuma
Hiroshi
H
D000818:Animals; D001119:Arginase / Q000378:metabolism*; D001120:Arginine / Q000378:metabolism; D002478:Cells, Cultured; D007511:Ischemia / Q000378:metabolism*; D008297:Male; D009092:Mucous Membrane / Q000378:metabolism; D009130:Muscle, Smooth / Q000098:blood supply / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D011073:Polyamines / Q000378:metabolism*; D011817:Rabbits; D001743:Urinary Bladder / Q000098:blood supply* / Q000378:metabolism*
D011073:Polyamines; D009569:Nitric Oxide; D001120:Arginine; D019001:Nitric Oxide Synthase; D001119:Arginase; D009955:Ornithine Decarboxylase