Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0406810 (NAME)
 13,345 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
 ...
PMID:Effects of nitric oxide synthase inhibitors on bone formation in rats. 943 Feb 37

Osteopenia is a significant problem associated with Diabetes mellitus. Osteopenia may result in an increased delay in healing of bone fractures and subsequently affect the quality of life. We evaluated the immunohistochemical localization of TRAIL and its receptor DR5 in the femoral bone of 10-week-old Sprague-Dawley male rats treated with sesame oil (control, group 1), streptozotocin (STZ), a diabetes inducer (group 2), L-NAME, a general inhibitor of NOS activity (group 3), L-arginine (group 4), (arginine acts as a NO substrate) and iNOS immunostaining in group 1 and group 4. Histological and histochemical findings showed decreased growth of metaphyseal cartilage (which was thinner), decreased osteoid surface, and reduced mineral apposition rate in STZ- and L-NAME-treated rats. These findings confirm that bone formation is impaired in diabetic osteopenia. L-arginine supplementation seems to prevent diabetes-induced bone alterations and preserve the calcification process, allowing synthesis of new bone matrix. The immunohistochemical study revealed increased immunostaining of TRAIL and DR5 in osteoblastic cells of the diaphysis (pre-metaphysis) and epiphysis treated with STZ and L-NAME, related to activation of osteoblastic apoptotic death, while the group receiving L-arginine was comparable to the control group and the higher indications of iNOS activity that may reflect its induction by L-arginine administration. The action of L-arginine suggests that increased NO synthesis and availability is potentially useful for effective prevention and treatment of diabetic osteopenia.
 ...
PMID:An in vivo experimental study on osteopenia in diabetic rats. 2069 68