title: High-dose ascorbic acid infusion abolishes chronic vasoconstriction and restores resting leg blood flow in healthy older men.
abstract: Resting whole leg blood flow and vascular conductance decrease linearly with advancing age in healthy adult men. The potential role of age-related increases in oxidative stress in these changes is unknown. Resting leg blood flow during saline and ascorbic acid infusion was studied in 10 young (25 +/- 1 yr) and 11 older (63 +/- 2 yr) healthy normotensive men. Plasma oxidized LDL, a marker of oxidative stress, was greater in the older men (P < 0.05). Absolute resting femoral artery blood flow at baseline (iv saline control infusion) was 25% lower in the older men (238 +/- 25 vs. 316 +/- 38 ml/min; P < 0.05), and it was inversely related to plasma oxidized LDL (r = -0.56, P < 0.01) in all subjects. Infusion of supraphysiological concentrations of ascorbic acid increased femoral artery blood flow by 37% in the older men (to 327 +/- 52 ml/min; P < 0.05), but not in the young men (352 +/- 41 ml/min; P = 0.28), thus abolishing group differences (P = 0.72). Mean arterial blood pressure was greater in the older men at baseline (86 +/- 4 vs. 78 +/- 2 mmHg; P < 0.05), but it was unaffected by ascorbic acid infusion (P >/= 0.70). As a result, the lower baseline femoral artery blood flow in the older men was mediated solely by a 32% lower femoral artery vascular conductance (P < 0.05). Baseline femoral vascular conductance also was inversely related to plasma oxidized LDL (r = -0.65, P < 0.01). Ascorbic acid increased femoral vascular conductance by 36% in the older men (P < 0.05) but not in the young men (P = 0.31). In conclusion, ascorbic acid infused at concentrations known to scavenge reactive oxygen species restores resting femoral artery blood flow in healthy older adult men by increasing vascular conductance. These results support the hypothesis that oxidative stress plays a major role in the reduced resting whole leg blood flow and increased leg vasoconstriction observed with aging in men.
authors.affiliation: Dept. of Integrative Physiology, Univ. of Colorado, Boulder, CO 80309, USA.
authors.forename: Kristen L
authors.initials: KL
authors.lastname: Jablonski
authors.forename: Douglas R
authors.initials: DR
authors.lastname: Seals
authors.forename: Iratxe
authors.initials: I
authors.lastname: Eskurza
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Monahan
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Donato
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000375:Aging / Q000097:blood / Q000378:metabolism*; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000097:blood; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000097:blood; D004837:Epinephrine / Q000097:blood; D005263:Femoral Artery / Q000000981:diagnostic imaging / Q000187:drug effects*; D016166:Free Radical Scavengers / Q000008:administration & dosage* / Q000097:blood; D006801:Humans; D007262:Infusions, Intravenous; D007866:Leg / Q000098:blood supply*; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D018616:Ultrasonography, Doppler, Duplex; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000097:blood
chemical_list: D019332:Endothelin-1; D016166:Free Radical Scavengers; D008077:Lipoproteins, LDL; D014662:Vasoconstrictor Agents; C099252:oxidized low density lipoprotein; D001205:Ascorbic Acid; D009638:Norepinephrine; D004837:Epinephrine