Kawano Keizo, Masuda Hitoshi, Yano Masataka, Kihara Kazunori, Sugimoto Akiko, Azuma Hiroshi
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.
J Urol. 2006 Jul;176(1):387-93. doi: 10.1016/S0022-5347(06)00515-5.
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.
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.
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.
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.
关于膀胱缺血后L-精氨酸的分解代谢知之甚少。我们研究了兔膀胱缺血后一氧化氮合酶、精氨酸酶和鸟氨酸脱羧酶活性、多胺生物合成以及产生一氧化氮能力的变化。
通过结扎单侧膀胱动脉造成膀胱缺血。在结扎后的不同时间点，即1、4、8、24、48和72小时，切除膀胱并进行取材测定。
组成型一氧化氮合酶、诱导型一氧化氮合酶、精氨酸酶和鸟氨酸脱羧酶活性随时间增加，在48小时达到峰值，全层结扎侧与未结扎侧之间无显著差异。缺血后精氨酸酶和鸟氨酸脱羧酶主要在肌层增加。此外，缺血48小时后肌层中的腐胺显著高于黏膜中的腐胺。结扎侧逼尿肌全层在24小时时的基线亚硝酸盐/硝酸盐生成量显著低于正常逼尿肌。然而，作为精氨酸酶抑制剂的去甲羟基精氨酸和L-精氨酸增加了缺血逼尿肌中的亚硝酸盐/硝酸盐生成量，而正常逼尿肌中则无变化。作为一氧化氮合酶抑制剂的甲基硝基精氨酸消除了去甲羟基精氨酸的这种增加作用。
与L-精氨酸分解代谢相关的酶参与了缺血性膀胱的早期事件。精氨酸酶可能有两个独立作用，即1）在缺血后肌肉损伤和重塑中激活精氨酸酶/鸟氨酸脱羧酶/多胺途径，以及2）通过限制一氧化氮合酶的L-精氨酸底物对一氧化氮生成进行内源性负调节。
