Efeito do óxido nítrico sobre fêmures e vértebras lombares de ratos orquiectomizados.
Abstract
Osteoporosis is attributed to an imbalance between bone formation and
resorption, followed by bone mass loss and microarchitectural deterioration, leading to
increased bone fragility and fracture risk. Nitric oxide (NO) is a signaling molecule with
important regulatory effects on bone cell function. Nitric oxide donor nitroglycerin has been
reported to alleviate ovariectomy-induced and corticosteroid-induced bone loss. The aim of
the present study was to investigate the effect of NO on cancellous and cortical bone of
orchiectomized rats. A total of 98 male Wistar rats (four months old) were randomly divided
in the following groups - Experiment I: intact treated with saline (stomacal gavage - gv),
orchiectomized treated with saline (gv), and orchiectomized treated with NO donor isosorbide
dinitrate - ISDN (gv); Experiment II: intact treated with saline (subcutaneous injection - sc),
orchiectomized treated with saline (sc), and orchiectomized treated with NO synthase
inhibitor NG-nitro-L-arginine-methylester - L-NAME (sc); Experiment III: intact treated with
saline (intraperitoneous injection - ip), orchiectomized treated with saline (ip), and
orchiectomized treated with NO precursor L-arginine (ip); Basal group: one group was killed
at the beginning of the study (four months old) and served as a baseline group. The animals
were killed after 8 weeks of treatment. At death, both femurs and lumbar vertebrae (L5-6)
were obtained from each rat, and changes in both cancellous and cortical bone mass and
biomechanical competence were assessed. The treatment with NO donor isosorbide dinitrate
protected the cortical bone mass of adult rats from the deleterious effects of castration. The
protective effect of ISDN treatment on the cancellous bone mass was not as significant as the
one observed on the cortical bone. The L-NAME treatment did not increase the deleterious
effects induced by orchiectomy in both cancellous and cortical bone mass. No effect was
observed with the L-arginine treatment, in the dose used in this study. In conclusion, this
study suggest that NO donor isosorbide dinitrate can be used in the future as an alternative
pharmacological strategy for the prevention of androgen deficiency osteoporosis, in men with
proven hypogonadism and in eugonadal men.