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Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats
H Tsukahara1, M Miura, S Tsuchida
1Department of Pediatrics, Fukui Medical School, Japan.
Abstract:
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.
Insights
Chronic administration of aminoguanidine (AG) in rats led to significant bone loss, suggesting nitric oxide (NO) is crucial for regulating bone resorption and maintaining bone mineral status.
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- Nitric oxide (NO) is a signaling molecule with diverse physiological roles.
- The role of NO in bone metabolism, particularly in growing animals, requires further elucidation.
Purpose of the Study:
- To investigate the impact of chronic nitric oxide (NO) blockade on bone mineral status in growing rats.
- To determine the specific contribution of NO to bone resorption and formation.
Main Methods:
- Oral administration of NG-nitro-L-arginine methyl ester (L-NAME) or aminoguanidine (AG) to growing rats for 4 weeks.
- Measurement of blood pressure, urinary NO2-/NO3- excretion, bone mineral mass (lumbar spine), and collagen cross-links.
- Assessment of serum osteocalcin levels.
Main Results:
- L-NAME induced hypertension and reduced urinary NO excretion; high doses slightly decreased bone mass.
- AG significantly reduced urinary NO excretion and induced spine osteopenia, an effect reversed by L-arginine.
- AG-induced osteopenia was linked to increased urinary collagen cross-links and normal serum osteocalcin.
Conclusions:
- Chronic AG administration disrupts bone resorption and formation balance, leading to decreased bone mass in growing rats.
- NO produced by inducible NO synthase plays a significant role in basal osteoclast bone degradation activity in vivo.