Prisby Rhonda D, Ramsey Michael W, Behnke Brad J, Dominguez James M, Donato Anthony J, Allen Matthew R, Delp Michael D
Division of Exercise Physiology, Department of Physiology and Pharmacology, and the Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, West Virginia 26506, USA.
J Bone Miner Res. 2007 Aug;22(8):1280-8. doi: 10.1359/jbmr.070415.
We determined whether aging diminishes bone blood flow and impairs endothelium-dependent vasodilation. Femoral perfusion was lower in old animals, as well as endothelium-dependent vasodilation and NO bioavailability. These effects could contribute to old age-related bone loss and the increased risk of fracture.
Aging has been shown to diminish bone blood flow in rats and humans. The purpose of this study was to determine whether blood flow to regions of the femur perfused primarily through the principal nutrient artery (PNA) are diminished with aging and whether this putative reduction in flow is associated with impaired endothelium-dependent vasodilation.
Blood flow was measured in conscious young adult (4-6 mo old) and aged (24-26 mo old) male Fischer-344 rats using radiolabeled microspheres. Endothelium-dependent vasodilation of the PNA was assessed in vitro using acetylcholine (ACh), whereas the contribution of the NO synthase (NOS) and cyclooxygenase (COX) signaling pathways to endothelium-dependent vasodilation was determined using the NOS and COX inhibitors L-NAME and indomethacin, respectively.
Femoral blood flow in the aged rats was 21% and 28% lower in the proximal and distal metaphyses, respectively, and 45% lower in the diaphyseal marrow. Endothelium-dependent vasodilation was reduced with old age (young: 83 +/- 6% maximal relaxation; aged: 62 +/- 5% maximal relaxation), whereas endothelium-independent vasodilation (sodium nitroprusside) was unaffected by age. The reduction in endothelium-dependent vasodilation was mediated through impairment of the NOS signaling pathway, which resulted in lower NO bioavailability (young: 168 +/- 56 nM; aged: 50 +/- 7 nM).
These data show that reductions in metaphyseal bone and diaphyseal marrow perfusion with old age are associated with diminished endothelium-dependent vasodilation through an impairment of the NOS mechanism. Such age-related changes in bone perfusion and vascular NO signaling could impact clinical bone loss, increase risk of fracture, and impair fracture healing in the elderly.
我们确定衰老是否会减少骨血流量并损害内皮依赖性血管舒张。老年动物的股骨灌注较低，内皮依赖性血管舒张和一氧化氮（NO）生物利用度也较低。这些影响可能导致与老年相关的骨质流失和骨折风险增加。
衰老已被证明会减少大鼠和人类的骨血流量。本研究的目的是确定主要通过主要营养动脉（PNA）灌注的股骨区域的血流量是否会随着衰老而减少，以及这种假定的血流量减少是否与内皮依赖性血管舒张受损有关。
使用放射性微球测量清醒的年轻成年（4 - 6月龄）和老年（24 - 26月龄）雄性Fischer - 344大鼠的血流量。使用乙酰胆碱（ACh）在体外评估PNA的内皮依赖性血管舒张，而分别使用一氧化氮合酶（NOS）和环氧化酶（COX）抑制剂L - NAME和吲哚美辛确定NOS和COX信号通路对内皮依赖性血管舒张的贡献。
老年大鼠近端和远端干骺端的股骨血流量分别降低了21%和28%，骨干骨髓血流量降低了45%。内皮依赖性血管舒张随着年龄增长而降低（年轻：最大舒张率83±6%；老年：最大舒张率62±5%），而内皮非依赖性血管舒张（硝普钠）不受年龄影响。内皮依赖性血管舒张的降低是通过NOS信号通路受损介导的，这导致NO生物利用度降低（年轻：168±56 nM；老年：50±7 nM）。
这些数据表明，随着年龄增长，干骺端骨和骨干骨髓灌注的减少与通过NOS机制受损导致的内皮依赖性血管舒张减弱有关。这种与年龄相关的骨灌注和血管NO信号变化可能影响临床骨质流失，增加老年人骨折风险，并损害骨折愈合。
