Tsukahara H, Miura M, Tsuchida S, Hata I, Hata K, Yamamoto K, Ishii Y, Muramatsu I, Sudo M
Department of Pediatrics, Fukui Medical School, Japan.
Am J Physiol. 1996 May;270(5 Pt 1):E840-5. doi: 10.1152/ajpendo.1996.270.5.E840.
We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) for 4 wk caused hypertension and a significant reduction in urinary NO2- and NO3- excretion. Four-week oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter blood pressure but caused a significant decrease in urinary NO2- and NO3-. Rats treated with L-NAME at doses of 20 and 50 mg/dl had normal bone mineral mass in the lumbar spine, but the highest dose (80 mg/dl) caused a slight decrease in bone mass. Chronic AG induced a significant spine osteopenia. This effect of AG was abolished by the simultaneous administration of L-arginine (2.0 g/dl). AG-induced osteopenia was associated with a significant increase in urine excretion of collagen cross-links with normal serum osteocalcin. These findings indicate that chronic AG administration can cause an imbalance between bone resorption and formation, resulting in a decrease in bone mass in growing rats, and suggest that NO produced by inducible NO synthase plays an important role in basal osteoclast bone degradation activity in vivo.
我们研究了慢性一氧化氮（NO）阻断对生长中大鼠骨矿物质状态的影响。口服NG-硝基-L-精氨酸甲酯（L-NAME）4周导致高血压，并使尿中NO2-和NO3-排泄显著减少。口服4周氨基胍（AG，饮用水中400mg/dl）未改变血压，但使尿中NO2-和NO3-显著减少。用20mg/dl和50mg/dl剂量的L-NAME处理的大鼠腰椎骨矿物质质量正常，但最高剂量（80mg/dl）导致骨量略有减少。慢性AG诱导显著的脊柱骨质减少。同时给予L-精氨酸（2.0g/dl）可消除AG的这种作用。AG诱导的骨质减少与胶原交联物尿排泄显著增加及血清骨钙素正常有关。这些发现表明，慢性给予AG可导致生长中大鼠骨吸收与形成失衡，从而导致骨量减少，并提示诱导型一氧化氮合酶产生的NO在体内破骨细胞基础骨降解活性中起重要作用。
