ESTROGEN--BONE BLOOD FLOW AND BONE MECHANICAL PROPERTIES

雌激素--骨血流量和骨机械特性

• 批准号: 6012597
• 负责人: JOHN T FLEMING
• 金额: $ 7.2万
• 依托单位: UNIVERSITY OF LOUISVILLE
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-08-01 至 2001-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6012597
• 关键词: acetylcholine; age difference; aging; animal old age; arterioles; biomechanics; bone; bone density; disease /disorder model; estrogens; female; gene expression; hormone therapy; laboratory rat; mechanical stress; musculoskeletal circulation; nitric oxide synthase; nonhuman therapy evaluation; norepinephrine; osteoporosis; ovariectomy; vascular endothelium; vasoconstriction; vasodilatation; vasodilation

Osteoporosis and the high incidence of bone fractures among women is a major public health issue. Among aged women, the rate of bone lose has been correlated with a decline in blood flow, suggesting that a decrease in bone blood flow contributes to the development of osteoporosis. This study will test the hypothesis that the decrease in bone blood flow with age is due to a dysfunctional vascular endothelium resulting from a decrease in estrogen levels. We propose the following: as estrogen level among females decrease with age, bone vascular endothelial cell function decreases, bone arterioles become more reactive to physiologic constrictor stimuli resulting in a decrease in bone blood flow and subsequently a decrease in bone density. This hypothesis will be tested by assessing bone vascular endothelial cell function among young (2 months), middle aged (5 months) and old (15 months) female rats, either treated or untreated with estrogen. Bone vascular endothelial cell function will be correlated with: (1) basal bone blood flow, (2) bone blood vessel vasoconstrictor reactivity, (3) plasma estrogen levels, and (4) bone biomechanical properties. Specific Aim #1 is to assess bone vascular endothelial cell function among female rats at three ages (2, 5 and 15 months). Specific Aim #2 is to assess the vasoconstrictor reactivity of bone arterioles from female rats at the same three ages, before and after removing the endothelium to evaluate the ability of the endothelium to produce dilator products in response to constrictor agonists. Specific Aim #3 is to determine if estrogen treatment will preserve vascular endothelial cell function, basal bone blood flow, vascular reactivity and bone mechanical properties among aging female rats. Specific Aim #4 is to determine if estrogen improves endothelial cell function by increasing the expression of nitric oxide synthase in the bone vasculature.

骨质疏松症和女性骨折的高发是一个主要的公共卫生问题。在老年妇女中，骨骼损失的速率与血液流动的下降有关，这表明骨血流量的降低有助于骨质疏松的发展。这项研究将检验以下假设：随着年龄的增长，骨血流的减少是由于雌激素水平降低引起的功能障碍血管内皮。我们提出以下建议：随着女性的雌激素水平随着年龄的增长而降低，骨血管内皮细胞功能降低，骨动脉对生理收缩刺激的反应性更高，导致骨血流量降低，随后降低了骨密度。该假设将通过评估年轻人（2个月），中年（5个月）和老年（15个月）雌性大鼠的骨血管内皮细胞功能进行检验，这些大鼠接受了雌激素的治疗​​或未治疗。骨血管内皮细胞功能将与：（1）基底骨血流，（2）骨血管血管血管血管收缩反应性，​​（3）血浆雌激素水平和（4）骨生物力学特性。具体目的＃1是评估三个年龄（2、5和15个月）的雌性大鼠骨血管内皮细胞功能。具体目的＃2是评估同一三个年龄段的雌性大鼠的血管收缩反应性，​​在去除内皮之前和之后，以评估内皮产生扩张产物的能力，以响应约束激动剂。具体目的＃3是确定雌激素治疗是否会保留血管内皮细胞功能，基底骨血流，血管反应性和衰老雌性大鼠的骨骼机械性能。 特定目的＃4是通过增加骨血管中一氧化氮合酶的表达来确定雌激素是否可以改善内皮细胞功能。

项目成果

Bone medullary arterioles from ovariectomized rats have smaller baseline diameters but normal eNOS expression and NO-mediated dilation.

卵巢切除大鼠的骨髓小动脉具有较小的基线直径，但 eNOS 表达和 NO 介导的扩张正常。

• DOI: 10.1016/j.lfs.2004.10.083
• 发表时间: 2005
• 期刊: Life sciences.
• 作者: Soukhova-O'Hare,Galia;Lei,Zhenmin;Falcone,JeffC;Barati,MichelleT;Feitelson,JeremyBA;Rao,ChV;Fleming,JohnT
• 通讯作者: Fleming,JohnT