Impaired peripheral vasodilation during graded systemic hypoxia in healthy older adults: role of the sympathoadrenal system.
Systemic hypoxia is a physiological and pathophysiological stress that activates the sympathoadrenal system and, in young adults, leads to peripheral vasodilation. We tested the hypothesis that peripheral vasodilation to graded systemic hypoxia is impaired in older healthy adults and that this age-associated impairment is due to attenuated β-adrenergic mediated vasodilation and elevated α-adrenergic vasoconstriction. Forearm blood flow was measured (Doppler ultrasound), and vascular conductance (FVC) was calculated in 12 young (24 ± 1 yr) and 10 older (63 ± 2 yr) adults to determine the local dilatory responses to graded hypoxia (90, 85, and 80% O2saturations) in control conditions, following local intra-arterial blockade of β-receptors (propranolol), and combined blockade of α- and β-receptors (phentolamine + propranolol). Under control conditions, older adults exhibited impaired vasodilation to hypoxia compared with young participants at all levels of hypoxia (peak ΔFVC at 80% [Formula: see text] = 4 ± 6 vs. 35 ± 8%;P< 0.01). During β-blockade, older adults actively constricted at 85 and 80% [Formula: see text] (peak ΔFVC at 80% [Formula: see text] = -13 ± 6%;P< 0.05 vs. control), whereas the response in the young was not significantly impacted (peak ΔFVC = 28 ± 8%). Combined α- and β-blockade increased the dilatory response to hypoxia in young adults; however, older adults failed to significantly vasodilate (peak ΔFVC at 80% [Formula: see text]= 12 ± 11% vs. 58 ± 11%;P< 0.05). Our findings indicate that peripheral vasodilation to graded systemic hypoxia is significantly impaired in older adults, which cannot be fully explained by altered sympathoadrenal control of vascular tone. Thus, the impairment in hypoxic vasodilation is likely due to attenuated local vasodilatory and/or augmented vasoconstrictor signaling with age.NEW & NOTEWORTHYWe found that the lack of peripheral vasodilation during graded systemic hypoxia with aging is not mediated by the sympathoadrenal system, strongly implicating local vascular control mechanisms in this impairment. Understanding these mechanisms may lead to therapeutic advances for improving tissue blood flow and oxygen delivery in aging and disease.
Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado; and.
Jennifer C
JC
Richards
Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado; and.
Anne R
AR
Crecelius
Medical Center of the Rockies Foundation, University of Colorado Health System, Loveland, Colorado.
Dennis G
DG
Larson
Medical Center of the Rockies Foundation, University of Colorado Health System, Loveland, Colorado.
Gary J
GJ
Luckasen
Human Cardiovascular Physiology Laboratory, Department of Health and Exercise Science, Center for Cardiovascular Research, Colorado State University, Fort Collins, Colorado; and Frank.Dinenno@ColoState.edu.
Frank A
FA
Dinenno
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology; D001784:Blood Gas Analysis; D001823:Body Composition; D002395:Catecholamines / Q000097:blood; D005260:Female; D005542:Forearm / Q000098:blood supply / Q000000981:diagnostic imaging; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D009131:Muscle, Smooth, Vascular / Q000254:growth & development / Q000502:physiology; D012039:Regional Blood Flow / Q000502:physiology; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D055815:Young Adult
D000317:Adrenergic alpha-Antagonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D002395:Catecholamines
adrenergic receptor; aging; blood flow; hypoxia; sympathetic nervous system