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首页> 外文期刊>Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research >Frequency-dependent effect of nitric oxide donor nitroglycerin on bone.
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Frequency-dependent effect of nitric oxide donor nitroglycerin on bone.

机译：一氧化氮供体硝酸甘油对骨骼的频率依赖性作用。

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摘要

Recently, we showed that supplementation with nitric oxide (NO) via donor nitroglycerin (NG) alleviated the ovariectomy and corticosteroid-induced bone loss in rats. In humans, high doses or frequent applications of NG (i.e., for angina) lead to rapid loss of its efficacy in relieving angina. To examine whether there is a similar effect on the loss of efficacy of NG on bone, we examined the frequency-dependent effects of NG on bone mineral density (BMD), bone mass, trabecular bone volumes (BV/TV), and blood pressure in rats. Thirty 7-month-old female Brown Norway rats underwent ovariectomy, and an additional six rats were sham-operated. The ovariectomized rats were treated either with vehicle (ovariectomized control), 17beta-estradiol (E2; positive control), or 0.2 mg NG (via dermal application) once, twice, or three times a day. Before and at the end of the 10-week treatment period, BMD of the lumbar spine was measured by dual-energy X-ray absorptiometric (DXA) scanning and expressed as a percentage change. BMD in ovariectomized rats was significantly lower (-2.5 +/- 2.0%) compared with the sham-operated rats (+6.3 +/- 5.3%; p < 0.01). Estrogen therapy completely abolished the ovariectomy-induced potential bone loss (+5.9 +/- 3.4%). Application of NG once daily also completely prevented (+6.2 +/- 2.8%; p < 0.01) the ovariectomy-induced bone loss (i.e., it was as effective as estrogen). However, the beneficial effects of NG on BMD were significantly reduced with increased frequency of application of NG (+1.9 +/- 2.1%, twice a day and -0.2 +/- 3.3% three times a day). Estrogen or once daily administration of NG preserved femur weights, BV/TV, and decreased urinary deoxypyridinoline levels as expected. However, a higher level of serum osteocalcin and bone-specific alkaline phosphatase levels were maintained only with once daily administration of NG. There were no adverse effects of these doses of NG on blood pressure, but a tendency to lower blood pressure was noticed with increased frequency of NG. These results confirmed our previous findings that NO donors counteract the bone loss associated with estrogen deficiency. However, these beneficial effects of maintaining BMD are lost with increased frequency of NG application.
机译：最近，我们显示通过供体硝酸甘油（NG）补充一氧化氮（NO）可以减轻大鼠卵巢切除术和皮质类固醇诱导的骨质流失。在人类中，高剂量或频繁使用NG（即用于心绞痛）会导致其缓解心绞痛的功效迅速丧失。为了检查NG对骨的功效丧失是否有类似的影响，我们检查了NG对骨矿物质密度（BMD），骨量，小梁骨体积（BV / TV）和血压的频率依赖性作用在大鼠中。 30只7个月大的雌性Brown Norway大鼠进行了卵巢切除术，另外6只大鼠进行了假手术。切除卵巢的大鼠每天用媒介物（切除卵巢的对照），17β-雌二醇（E2;阳性对照）或0.2 mg NG（经皮应用）治疗一次，两次或三次。在10周治疗期之前和结束时，通过双能X射线吸收法（DXA）扫描测量腰椎的BMD，并以百分比变化表示。与假手术大鼠（+6.3 +/- 5.3％; p <0.01）相比，去卵巢大鼠的BMD显着降低（-2.5 +/- 2.0％）。雌激素疗法完全消除了卵巢切除术引起的潜在骨质流失（+5.9 +/- 3.4％）。每天一次使用NG还可以完全防止（+6.2 +/- 2.8％; p <0.01）卵巢切除术引起的骨质流失（即与雌激素一样有效）。但是，NG对BMD的有益作用随NG施用频率的增加而显着降低（每天两次，+ 1.9 +/- 2.1％，每天三次，-0.2 +/- 3.3％）。如预期的那样，雌激素或每天一次的NG可以保持股骨重量，BV / TV并降低尿中的脱氧吡啶啉水平。但是，仅每天一次施用NG才能维持较高水平的血清骨钙素和骨特异性碱性磷酸酶水平。这些剂量的NG对血压没有不利影响，但是随着NG频率的增加，人们注意到有降低血压的趋势。这些结果证实了我们以前的发现，即没有供体可以抵消与雌激素缺乏有关的骨质流失。然而，随着NG应用频率的增加，保持BMD的这些有益效果就消失了。

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