Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and no bioavailability in rats

Rhonda D. Prisby, Michael W. Ramsey, Brad J. Behnke, James M. Dominguez, Anthony J. Donato, Matthew Allen, Michael D. Delp

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)1280-1288
Number of pages9
JournalJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
Volume22
Issue number8
DOIs
StatePublished - Aug 2007

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Vasodilation
Biological Availability
Endothelium
Nitric Oxide Synthase
Bone and Bones
Perfusion
Thigh
Arteries
Bone Marrow
Food
Fracture Healing
Cyclooxygenase Inhibitors
NG-Nitroarginine Methyl Ester
Inbred F344 Rats
Nitroprusside
Prostaglandin-Endoperoxide Synthases
Microspheres
Indomethacin
Femur
Osteoporosis

Keywords

  • Artery
  • Marrow blood flow
  • Trabecular BV/TV

ASJC Scopus subject areas

  • Surgery

Cite this

Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and no bioavailability in rats. / Prisby, Rhonda D.; Ramsey, Michael W.; Behnke, Brad J.; Dominguez, James M.; Donato, Anthony J.; Allen, Matthew; Delp, Michael D.

In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, Vol. 22, No. 8, 08.2007, p. 1280-1288.

Research output: Contribution to journalArticle

Prisby, Rhonda D. ; Ramsey, Michael W. ; Behnke, Brad J. ; Dominguez, James M. ; Donato, Anthony J. ; Allen, Matthew ; Delp, Michael D. / Aging reduces skeletal blood flow, endothelium-dependent vasodilation, and no bioavailability in rats. In: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2007 ; Vol. 22, No. 8. pp. 1280-1288.
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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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AU - Prisby, Rhonda D.

AU - Ramsey, Michael W.

AU - Behnke, Brad J.

AU - Dominguez, James M.

AU - Donato, Anthony J.

AU - Allen, Matthew

AU - Delp, Michael D.

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N2 - 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.

AB - 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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KW - Trabecular BV/TV

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