Effects of nitric oxide synthase inhibitors on bone formation in rats

C. H. Turner, I. Owan, D. S. Jacob, R. McClintock, M. Peacock

Research output: Contribution to journalArticle

66 Citations (Scopus)

Abstract

NO is synthesized from L-arginine by at least three isoforms of nitric oxide synthase (NOS) and is known to function as a vasodilator and neurotransmitter. NO is produced by bone cells but its function in bone biology is, as yet, unclear. We hypothesized that NOS mediates bone formation in remodeling regions of the skeleton. We studied the effects of two NOS inhibitors: N(G)-nitro-L-arginine methyl ester (L-NAME), which is a general inhibitor of NOS activity and is known to inhibit the vasodilatory effects of the endothelial NOS (eNOS) isoform; and aminoguanidine, which is a selective inhibitor of the inducible NOS (iNOS) isoform. Our hypothesis was tested by treating rats with NOS inhibitors and measuring bone formation rates in the tibial epiphysis and diaphysis. Bone formation indices were measured using standard bone histomorphometry. L-NAME treatment significantly raised mean arterial blood pressure (MAP). This effect was partially reversed by addition of L-arginine. Aminoguanidine had no significant effect on MAP, indicating that it did not block eNOS. The treatments also had substantial effects on bone formation in remodeling trabecular bone. L-NAME did not significantly change trabecular bone formation rate, whereas aminoguanidine reduced bone formation rate in the tibial epiphysis by 79% compared with control. This reduction was completely reversed by L-arginine, suggesting that bone formation during remodeling is, in part, mediated through L-arginine metabolism. No effect of aminoguanidine on bone formation was seen in the tibial diaphysis, a site that undergoes minimal bone remodeling. This finding suggests that the L-arginine-NO pathway is important in bone remodeling.

Original languageEnglish (US)
Pages (from-to)487-490
Number of pages4
JournalBone
Volume21
Issue number6
DOIs
StatePublished - Dec 1997

Fingerprint

Osteogenesis
Nitric Oxide Synthase
NG-Nitroarginine Methyl Ester
Arginine
Arterial Pressure
Diaphyses
Protein Isoforms
Epiphyses
Bone Remodeling
Bone and Bones
Nitric Oxide Synthase Type III
Nitric Oxide Synthase Type II
Vasodilator Agents
Skeleton
Neurotransmitter Agents
pimagedine

Keywords

  • Aminoguanidine
  • Bone density
  • N(G)-nitro-L-arginine methyl ester
  • Nitric oxide
  • Nitric oxide synthase
  • Osteoblasts

ASJC Scopus subject areas

  • Physiology
  • Hematology

Cite this

Turner, C. H., Owan, I., Jacob, D. S., McClintock, R., & Peacock, M. (1997). Effects of nitric oxide synthase inhibitors on bone formation in rats. Bone, 21(6), 487-490. https://doi.org/10.1016/S8756-3282(97)00202-0

Effects of nitric oxide synthase inhibitors on bone formation in rats. / Turner, C. H.; Owan, I.; Jacob, D. S.; McClintock, R.; Peacock, M.

In: Bone, Vol. 21, No. 6, 12.1997, p. 487-490.

Research output: Contribution to journalArticle

Turner, CH, Owan, I, Jacob, DS, McClintock, R & Peacock, M 1997, 'Effects of nitric oxide synthase inhibitors on bone formation in rats', Bone, vol. 21, no. 6, pp. 487-490. https://doi.org/10.1016/S8756-3282(97)00202-0
Turner CH, Owan I, Jacob DS, McClintock R, Peacock M. Effects of nitric oxide synthase inhibitors on bone formation in rats. Bone. 1997 Dec;21(6):487-490. https://doi.org/10.1016/S8756-3282(97)00202-0
Turner, C. H. ; Owan, I. ; Jacob, D. S. ; McClintock, R. ; Peacock, M. / Effects of nitric oxide synthase inhibitors on bone formation in rats. In: Bone. 1997 ; Vol. 21, No. 6. pp. 487-490.
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