Aging Reduces Skeletal Blood Flow, Endothelium-Dependent Vasodilation, and NO Bioavailability in Rats

Authors

  • Rhonda D Prisby,

    1. 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, USA
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  • Michael W Ramsey,

    1. Department of Physical Education, Exercise, and Sports Sciences, East Tennessee State University, Johnson City, Tennessee, USA
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  • Brad J Behnke,

    1. 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, USA
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  • James M Dominguez II,

    1. 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, USA
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  • Anthony J Donato,

    1. Department of Integrative Physiology, University of Colorado, Boulder, Colorado, USA
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  • Matthew R Allen,

    1. Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana, USA
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  • Michael D Delp PhD

    Corresponding author
    1. 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, USA
    • Division of Exercise Physiology Center for Interdisciplinary Research in Cardiovascular Sciences, West Virginia University School of Medicine, Morgantown, WV 26506, USA
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  • The authors state that they have no conflicts of interest.

Abstract

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.

Introduction: 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.

Materials and Methods: 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.

Results: 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).

Conclusions: 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.

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