Effects of Aging and Exercise Training on Vasomotor Function of Bone Resistance Arteries and Bone Blood Flow

Abstract

Adequate skeletal perfusion is necessary to maintain bone remodeling processes, and decrements in bone arterial function and regional blood flow may lead to conditions such as osteoporosis. Aging elicits progressive bone loss, associated with impaired bone vasomotor function and perfusion, that can lead to osteoporosis. Although these age‐related adaptations are ameliorated via exercise training, the specific mechanisms underlying exercise‐induced alterations of bone vasomotor function with aging remain largely unknown. The purpose of this study was to elucidate the age‐ and exercise‐induced vasomotor adaptations of the bone principal nutrient artery and subsequent alterations in bone blood flow.Young and old male Fischer‐344 rats underwent treadmill exercise training (15 m/min, 15° incline, 1hr/day, 5 days/wk for 10–12 wks) or remained sedentary in cages. At the end of the experimental period, the femoral principal nutrient artery (PNA) was isolated, cannulated, and pressurized for vascular response studies. Vasoconstrictor responses of the PNA were assessed in vitro using α‐adrenergic agonist phenylephrine (PE, 10−9–10−4 M), receptor‐independent potassium chloride (KCl, 10–100 mM) and myogenic responsiveness to increasing intraluminal pressure (0 to 140 cmH2O). Endothelium‐dependent (ACh, 10−9–10−4 M) and ‐independent (Dea‐NONOate, 10−9–10−4 M) vasodilator responses were also evaluated. Additionally, regional blood flow to the femur was measured at rest and during exercise using radiolabeled microspheres.Vasomotor responses to agonists for constriction (PE, KCl) and dilation (ACh, Dea‐NONOate) decreased with aging. In contrast, myogenic responsiveness in old rats was greater compared with young rats (p<0.05). Vasoconstrictor response to KCl was greater after training in both young and old rats as compared to the sedentary rats. Exercise‐trained old rats also showed increased vasoconstrictor responses to PE and myogenic responsiveness; however, no significant difference was shown in young rats (p<0.05). Exercise training enhanced endothelium‐dependent vasodilation in both young and old rats; however, no significant exercise effect was observed in endothelium‐independent vasodilation (p<0.05). Regional femur blood flow to the proximal and distal metaphysis and epiphysis, as well as diaphyseal marrow, was lower in aged rats compared to young rats at rest. However, exercise‐trained old rats showed significantly increased regional blood flow during exercise compared with old SED rats (p<0.05).These results demonstrate vasomotor responses are impaired in the femoral PNA from aged rats; however, endurance training intervention at advancing age can reverse vasomotor deficits including vasoconstrictor and vasodilator response in bone resistance arteries and enhance regional bone and marrow blood flow. Such changes in bone and marrow perfusion could play an important role in enhancing the quality and strength of bone in old age following exercise training.Support or Funding InformationNIH grant AG055029