title: Role of {alpha}1-adrenergic vasoconstriction in the regulation of skeletal muscle blood flow with advancing age.
abstract: alpha(1)-Adrenergic vasoconstriction during dynamic leg exercise is diminished in younger individuals, although the extent of this exercise-induced "sympatholysis" in the elderly remains uncertain. Thus, in nine young (25 +/- 1 yr) and six older (72 +/- 2 yr) healthy volunteers, we evaluated changes in leg blood flow (ultrasound Doppler) during blood flow-adjusted intra-arterial infusion of phenylephrine (PE; a selective alpha(1)-adrenergic agonist) at rest and during knee-extensor leg exercise at 20, 40, and 60% of maximal work rate (WR(max)). To probe the potential contributors to exercise-induced changes in alpha(1)-adrenergic receptor sensitivity, exercising leg O(2) consumption (Vo(2)) and lactate efflux were also evaluated (n = 10). At rest, the PE-induced vasoconstriction (i.e., decrease in leg blood flow) was diminished in older (-37 +/- 3%) compared with young (-54 +/- 4%) subjects. During exercise, the magnitude of alpha(1)-adrenergic vasoconstriction in the active leg decreased in both groups. However, compared with young, older subjects maintained a greater vasoconstrictor response to PE at 40% WR(max) (-14 +/- 3%, older; -7 +/- 2%, young) and 60% WR(max) (-11 +/- 3%, older; -4 +/- 3%, young). It is possible that this observation may be attributed to lower absolute work rates in the older group, because, for a similar absolute work rate ( approximately 10 W) and leg Vo(2) ( approximately 0.36 l/min), vasoconstriction to PE was not different between groups (-14 +/- 3%; older; -17 +/- 5%, young). Together, these data challenge the concept of reduced sympatholysis in the elderly, suggesting instead that the inhibition of alpha(1)-adrenergic vasoconstriction in the exercising leg is associated with work performed and, therefore, more closely related to the rate of oxidative metabolism than to age per se.
authors.affiliation: Deptartment of Medicine, Univers9ty of Utah, VAMC SLC, Bldg. 2, Salt Lake City, UT 84132, USA. walter.wray@hsc.utah.edu
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Steven K
authors.initials: SK
authors.lastname: Nishiyama
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage; D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging; D001783:Blood Flow Velocity / Q000187:drug effects; D015444:Exercise; D005260:Female; D006801:Humans; D007261:Infusions, Intra-Arterial; D019344:Lactic Acid / Q000097:blood; D017078:Laser-Doppler Flowmetry; D008297:Male; D009119:Muscle Contraction; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism; D010101:Oxygen Consumption; D010656:Phenylephrine / Q000008:administration & dosage / Q000494:pharmacology*; D011433:Propranolol / Q000008:administration & dosage; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism; D012039:Regional Blood Flow / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology*; D055815:Young Adult
chemical_list: D058646:Adrenergic alpha-1 Receptor Agonists; D000316:Adrenergic alpha-Agonists; D000319:Adrenergic beta-Antagonists; D018340:Receptors, Adrenergic, alpha-1; D014662:Vasoconstrictor Agents; D010656:Phenylephrine; D019344:Lactic Acid; D011433:Propranolol