title: Angiotensin II in the elderly: impact of angiotensin II type 1 receptor sensitivity on peripheral hemodynamics.
abstract: Exercise hyperemia is attenuated in the elderly, which may be attributed to local vasoregulatory pathways within the skeletal muscle vasculature. Therefore, we sought to determine whether healthy aging is associated with changes in angiotensin II (Ang II) receptor sensitivity through measurements of leg blood flow in resting and exercising skeletal muscle. In 12 (n=6 young, 24+/-1 years; n=6 older, 68+/-3 years) healthy volunteers, we determined changes in leg blood flow (ultrasound Doppler) before and during intra-arterial infusion of Ang II (0.8 ng/mL of leg blood flow per minute). Heart rate, arterial blood pressure, common femoral artery diameter, and mean blood velocity were measured at rest and during knee-extensor exercise at 20% and 40% of the maximal work rate (WR(max)). At rest, Ang II infusion decreased leg blood flow to a greater extent in older (-61+/-8%) subjects compared with younger subjects (-31+/-5%). Compared with rest, Ang II-mediated vasoconstriction (leg blood flow) during exercise was diminished in both older and younger subjects at 20% (older: -7+/-5%; younger: -21+/-2%) and 40% WR(max) (older: -5+/-4%; younger: -9+/-3%). These data identify a clear age-related hypersensitivity to Ang II in the resting leg, which may contribute to the recognized decrement in leg blood flow in this cohort. However, the diminished vasoconstriction to Ang II during exercise suggests that the elevation in Ang II type 1 receptor sensitivity documented at rest does not contribute significantly to the blunted exercise hyperemia experienced with advancing age.
authors.affiliation: Department of Medicine, University of California San Diego, La Jolla, CA 92093-0623, USA. dwray@ucsd.edu
authors.forename: D Walter
authors.initials: DW
authors.lastname: Wray
authors.forename: Steven K
authors.initials: SK
authors.lastname: Nishiyama
authors.forename: Ryan A
authors.initials: RA
authors.lastname: Harris
authors.forename: Russell S
authors.initials: RS
authors.lastname: Richardson
mesh_terms: D000328:Adult; D000368:Aged; D000375:Aging / Q000502:physiology*; D000804:Angiotensin II / Q000008:administration & dosage / Q000097:blood*; D001783:Blood Flow Velocity / Q000187:drug effects / Q000502:physiology; D015444:Exercise / Q000502:physiology*; D006801:Humans; D006940:Hyperemia / Q000503:physiopathology; D007866:Leg / Q000098:blood supply; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology*; D012146:Rest / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000097:blood*
chemical_list: D044140:Receptor, Angiotensin, Type 1; D014662:Vasoconstrictor Agents; D000804:Angiotensin II