title: The role of nitric oxide in passive leg movement-induced vasodilatation with age: insight from alterations in femoral perfusion pressure.
abstract: The passive leg movement (PLM) model is a novel approach to assess vascular function. Increasing femoral perfusion pressure (FPP) by moving from the supine to the upright-seated posture augments the vasodilatory response to PLM in the young, with no effect in the old, but whether this augmented vasodilatation is nitric oxide (NO) dependent is unknown. Using an intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) to inhibit nitric oxide synthase (NOS), the posture-induced increases in the PLM responses in the young were nearly ablated, with no effect of NOS inhibition in the old. Therefore, PLM in combination with alterations in posture can be used to determine changes in NO-mediated vasodilatation with age, and thus, may be a clinically useful tool for assessing NO bioavailability across the human lifespan. We sought to better understand the contribution of nitric oxide (NO) to passive leg movement (PLM)-induced vasodilatation with age, with and without a posture-induced increase in femoral perfusion pressure (FPP). PLM was performed in eight young (24 ± 1 years) and eight old (74 ± 3 years) healthy males, with and without NO synthase inhibition via intra-arterial infusion of N(G) -monomethyl-L -arginine (L -NMMA) into the common femoral artery in both the supine and upright-seated posture. Central and peripheral haemodynamic responses were determined second-by-second with finger photoplethysmography and Doppler ultrasound, respectively. PLM-induced increases in heart rate, stroke volume, cardiac output and reductions in mean arterial pressure were similar between age groups and conditions. In the young, L -NMMA attenuated the peak change in leg vascular conductance (ΔLVCpeak ) in both the supine (control: 7.4 ± 0.9; L -NMMA: 5.2 ± 1.1 ml min(-1) mmHg(-1) , P < 0.05) and upright-seated (control: 12.3 ± 2.0; L -NMMA: 6.4 ± 1.0 ml min(-1) mmHg(-1) , P < 0.05) posture, with no significant change in the old (supine control: 4.2 ± 1.3; supine L -NMMA: 3.4 ± 0.8; upright-seated control: 4.5 ± 0.8; upright-seated L -NMMA: 3.4 ± 0.8 ml min(-1) mmHg(-1) , P > 0.05). Increased FPP augmented the ΔLVCpeak in the young control condition only (P < 0.05). In the upright-seated posture, NOS inhibition attenuated the FPP-induced augmentation of rapid vasodilatation in the young (control: 1.25 ± 0.23; L -NMMA: 0.74 ± 0.11 ml min(-1) mmHg(-1) s(-1) ; P < 0.05), but not the old (control: 0.37 ± 0.07; L -NMMA: 0.25 ± 0.07 ml ml min(-1) mmHg(-1) s(-1) ; P > 0.05). These data reveal that greater FPP increases the role of NO in PLM-induced vasodilatation in the young, but not the old, due to reduced NO bioavailability with age. Therefore, PLM involving alterations in posture may be useful to determine changes in NO bioavailability with age.
authors.affiliation: Geriatric Research, Education, and Clinical Centre, VAMC, Salt Lake City, UT, USA.|Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: H Jonathan
authors.initials: HJ
authors.lastname: Groot
authors.affiliation: Geriatric Research, Education, and Clinical Centre, VAMC, Salt Lake City, UT, USA.|Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Joel D
authors.initials: JD
authors.lastname: Trinity
authors.affiliation: Geriatric Research, Education, and Clinical Centre, VAMC, Salt Lake City, UT, USA.|Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Gwenael
authors.initials: G
authors.lastname: Layec
authors.affiliation: Geriatric Research, Education, and Clinical Centre, VAMC, Salt Lake City, UT, USA.|Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Rossman
authors.affiliation: Health and Exercise Sciences Department, Skidmore College, Saratoga Springs, NY, USA.
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Ives
authors.affiliation: Department of Anesthesia, University of Utah, Salt Lake City, UT, USA.
authors.forename: David E
authors.initials: DE
authors.lastname: Morgan
authors.affiliation: Department of Anesthesia, University of Utah, Salt Lake City, UT, USA.
authors.forename: Amber
authors.initials: A
authors.lastname: Bledsoe
authors.affiliation: Geriatric Research, Education, and Clinical Centre, VAMC, Salt Lake City, UT, USA.|Department of Exercise and Sport Science, University of Utah, Salt Lake City, UT, USA.|Department of Internal Medicine, University of Utah, Salt Lake City, UT, USA.
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D005263:Femoral Artery / Q000502:physiology*; D006439:Hemodynamics; D006801:Humans; D007866:Leg / Q000098:blood supply* / Q000502:physiology*; D008297:Male; D009068:Movement / Q000502:physiology; D009569:Nitric Oxide / Q000502:physiology*; D014664:Vasodilation / Q000502:physiology*; D055815:Young Adult; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide