Effect of nitric oxide synthase inhibitors on bone metabolism in
growing rats.
Tsukahara, Hirokazu, Masakazu Miura, Shinya Tsuchida, Ikue Hata,
Keishi Hata, Kazutaka Yamamoto, Yasushi Ishii, Ikunobu Muramatsu, and
Masakatsu Sudo.
Department of Pediatrics, Fukui Medical School, Fukui, Japan,
Department of Research and Development, Mitsubishi Kagaku Bio
-Clinical Laboratories Inc., Tokyo, Japan, Department of Radiology,
Fukui Medical School, Fukui, Japan, Department of Pharmacology, Fukui
Medical School, Fukui, Japan
APStracts 2:0256E, 1995.
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 weeks caused hypertension and a
significant reduction in urinary nitrite/nitrate excretion. Four-week
oral aminoguanidine (AG, 400 mg/dl of drinking water) did not alter
blood pressure but caused a significant decrease in urinary
nitrite/nitrate. 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 crosslinks 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.
Received 14 September 1995; accepted in final form 6 December
1995.
APS Manuscript Number E446-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 23 December 95