title: Effect of nitric oxide synthase inhibitors on bone metabolism in growing rats.
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.
authors.affiliation: Department of Pediatrics, Fukui Medical School, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Tsukahara
authors.forename: M
authors.initials: M
authors.lastname: Miura
authors.forename: S
authors.initials: S
authors.lastname: Tsuchida
authors.forename: I
authors.initials: I
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Hata
authors.forename: K
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ishii
authors.forename: I
authors.initials: I
authors.lastname: Muramatsu
authors.forename: M
authors.initials: M
authors.lastname: Sudo
mesh_terms: D015502:Absorptiometry, Photon; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000378:metabolism*; D004731:Endotoxins / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D008161:Lumbosacral Region; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009566:Nitrates / Q000652:urine; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009573:Nitrites / Q000652:urine; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000187:drug effects / Q000378:metabolism
chemical_list: D004731:Endotoxins; D006146:Guanidines; D009566:Nitrates; D009573:Nitrites; D019001:Nitric Oxide Synthase; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester