EFFECTS OF NITRIC-OXIDE SYNTHASE INHIBITORS ON BONE-FORMATION IN RATS

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 ne urotransmitter. NO is produced by hone cells but its function in bone biology is, as Set, unclear. We hypothesized that NOS mediates bone fo rmation in remodeling regions of the skeleton, We studied the effects of two NOS inhibitors: N-G-nitro-L-arginine methyl ester (L-NAME), whi ch is a general inhibitor of NOS activity and is known to inhibit the vasodilatory effects of the endothelial NOS (eNOS) isoform; and aminog uanidine, which is a selective inhibitor of the inducible NOS (MOS) is oform, Our hypothesis was tested by treating rats with NOS inhibitors and measuring bone formation rates in the tibial epiphysis and diaphys is. Bone formation indices were measured using standard bone histomorp hometry. L-NAME treatment significantly raised mean arterial blood pre ssure (MAP), This effect was partially reversed by addition of L-argin ine, Aminoguanidine had no significant effect on MAP, indicating that it did not block eNOS, Tile treatments also had substantial effects on bone formation in remodeling trabecular bone, L-NAME did not signific antly change trabecular bone formation rate, whereas aminoguanidine re duced bone formation rate in the tibial epiphysis by 79% compared with control. This reduction was completely reversed by L-arginine, sugges ting that bone formation during remodeling is, in part, mediated throu gh L-arginine metabolism, No effect of aminoguanidine on bone formatio n was seen in the tibial diaphysis, a site that undergoes minimal bone remodeling, This finding suggests that the L-arginine-NO pathway is i mportant in bone remodeling, (C) 1997 by Elsevier Science Inc, All rig hts reserved.