title: Ageing and leg postjunctional alpha-adrenergic vasoconstrictor responsiveness in healthy men.
abstract: Muscle sympathetic vasoconstrictor nerve activity increases with advancing age, but does not result in elevated forearm vasoconstrictor tone because of a selective reduction in alpha1-adrenoceptor responsiveness. In contrast, the leg circulation of older adults is under greater tonic sympathetic vasoconstriction, but it is unclear whether alpha-adrenoceptor responsiveness is altered with age. In the present study, we tested the hypothesis that postjunctional alpha-adrenergic vasoconstrictor responsiveness is reduced in the leg circulation with age. We measured femoral blood flow (Doppler ultrasound) and calculated the femoral vascular conductance (FVC) responses to alpha-adrenoceptor stimulation during local blockade of beta-adrenoceptors in 12 young (24 +/- 1 year) and seven healthy older men (62 +/- 2 year). Whole-leg vasoconstrictor responses to local intrafemoral artery infusions of tyramine (evokes noradrenaline (NA) release), phenylephrine (alpha1-agonist) and dexmedetomidine (alpha2-agonist) were assessed. Consistent with previous data, resting femoral blood flow and FVC were approximately 30% lower in older compared with young men (P < 0.05). Maximal vasoconstrictor responses to tyramine (-30 +/- 3 versus -41 +/- 3%), phenylephrine (-25 +/- 4 versus -45 +/- 5%), and dexmedetomidine (-22 +/- 4 versus -44 +/- 3%) were all significantly lower in older compared with young men (all P < 0.05). Our results indicate that human ageing is associated with a reduction in leg postjunctional alpha-adrenoceptor responsiveness to endogenous NA release, and this reduction is evident for both alpha1- and alpha2-adrenoceptors. However, given that basal leg vascular conductance is reduced with age and is primarily mediated by sympathetic vasoconstriction, impaired alpha-adrenoceptor responsiveness does not negate the ability of the sympathetic nervous system to evoke greater tonic vasoconstriction in the leg vasculature of older men.
authors.affiliation: Department of Health and Exercise Science, Colorado State University, 220 Moby-B Complex, Fort Collins, CO 80523-1582, USA.
authors.forename: Erica G
authors.initials: EG
authors.lastname: Smith
authors.forename: Wyatt F
authors.initials: WF
authors.lastname: Voyles
authors.forename: Brett S
authors.initials: BS
authors.lastname: Kirby
authors.forename: Rachel R
authors.initials: RR
authors.lastname: Markwald
authors.forename: Frank A
authors.initials: FA
authors.lastname: Dinenno
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000328:Adult; D000368:Aged; D000375:Aging / Q000378:metabolism / Q000502:physiology*; D001783:Blood Flow Velocity / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005263:Femoral Artery / Q000187:drug effects* / Q000294:innervation / Q000378:metabolism; D006801:Humans; D017078:Laser-Doppler Flowmetry; D007866:Leg / Q000098:blood supply*; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D012016:Reference Values; D012107:Research Design; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism; D014439:Tyramine / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D058647:Adrenergic alpha-2 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D018340:Receptors, Adrenergic, alpha-1; D018341:Receptors, Adrenergic, alpha-2; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D020927:Dexmedetomidine; D009638:Norepinephrine; D014439:Tyramine