title: Modulation of postjunctional α-adrenergic vasoconstriction during exercise and exogenous ATP infusions in ageing humans.
abstract: The ability to modulate sympathetic α-adrenergic vasoconstriction in contracting muscle is impaired with age. In young adults, adenosine triphosphate (ATP) has been shown to blunt sympathetic vasoconstrictor responsiveness similar to exercise. Therefore, we tested the hypothesis that modulation of postjunctional α-adrenergic vasoconstriction to exogenous ATP is impaired in ageing humans.We measured forearm blood flow (FBF; Doppler ultrasound) and calculated vascular conductance (FVC) to intra-arterial infusions of phenylephrine (α₁-agonist) and dexmedetomidine (α₂-agonist) during rhythmic handgrip exercise (15% MVC), a control non-exercise vasodilator condition (adenosine), and ATP infusion in seven older (64 ± 3 years) and seven young (22 ± 1 years) healthy adults. Forearm hyperaemia was matched across all vasodilatating conditions. During adenosine, forearm vasoconstrictor responses to direct α₁-stimulation were lower in older compared with young adults (ΔFVC=-25 ± 3% vs. -41 ± 5%; P <0.05), whereas the responses to α₂-stimulation were not different (-35±6% vs. -44 ± 8%; NS). During exercise, α₁-mediated vasoconstriction was significantly blunted compared with adenosine in both young (-9 ± 2% vs. -41 ± 5%) and older adults (-15 ± 2% vs. -25 ± 3%); however, the magnitude of sympatholysis was reduced in older adults (32 ± 13 vs. 74 ± 8%; P <0.05). Similarly, α₂-mediated vasoconstriction during exercise was significantly blunted in both young (-15 ± 4% vs. -44 ± 8%) and older adults (-26 ± 3% vs. -35 ± 6%), however the magnitude of sympatholysis was reduced in older adults (19 ± 8% vs. 60 ± 10%; P <0.05). During ATP, both α₁- and α₂-mediated vasoconstriction was nearly abolished in young and older adults (ΔFVC ∼ -5%), and the magnitude of sympatholysis was similar in both age groups (∼85-90%). Our findings indicate that the ability to modulate postjunctional α-adrenergic vasoconstriction during exercise is impaired with age, whereas the sympatholytic effect of exogenous ATP is preserved. Thus, if impairments in vascular control during exercise in older adults involve vasoactive ATP, we speculate that circulating ATP is reduced with advancing age.
authors.affiliation: Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Vascular Physiology Research Group, Colorado State University, Fort Collins, CO 80523-1582, USA.
authors.forename: Brett S
authors.initials: BS
authors.lastname: Kirby
authors.forename: Anne R
authors.initials: AR
authors.lastname: Crecelius
authors.forename: Wyatt F
authors.initials: WF
authors.lastname: Voyles
authors.forename: Frank A
authors.initials: FA
authors.lastname: Dinenno
mesh_terms: D000241:Adenosine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000008:administration & dosage*; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000368:Aged; D000375:Aging / Q000187:drug effects / Q000502:physiology*; D020927:Dexmedetomidine / Q000494:pharmacology; D015444:Exercise / Q000502:physiology*; D005260:Female; D005542:Forearm / Q000098:blood supply* / Q000000981:diagnostic imaging / Q000502:physiology; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D006940:Hyperemia / Q000188:drug therapy / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000098:blood supply / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D018608:Ultrasonography, Doppler; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D000316:Adrenergic alpha-Agonists; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D020927:Dexmedetomidine; D000255:Adenosine Triphosphate; D000241:Adenosine