Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats

We examined the effects of chronic nitric oxide (NO) blockade on bone mineral status in growing rats. Oral administration of N(G)-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.