Influence of Age and Heightened Sympathetic Tone on Lower Extremity FMD

Abstract

It has been shown previously that application of an acute sympathetic stimulus attenuates brachial artery flow-mediated dilation (FMD). However, it is unclear whether lower limb FMD is influenced by a sympathetic stimulus, whether this effect is altered by advancing age, and whether mechanisms underlying sympathetically-mediated blunted FMD involve the shear stimulus and/or the dilatory response. PURPOSE: To determine the influence of age and acute sympathetic stimulation on popliteal artery FMD in healthy women. METHODS: Popliteal artery diameter and velocity (Doppler ultrasound) as well as blood pressure and heart rate responses were assessed in 8 young (24±4 yrs) and 8 older (69±4 yrs) women following 5 minutes of distal calf occlusion (FMD), 3 minutes of hand immersion in ice water (cold pressor test, CPT) and 5 minutes of distal calf occlusion combined with hand immersion in ice water (FMD+CPT). Popliteal artery diameter was measured at rest, during occlusion, and as the peak diameter observed post-occlusion; time-averaged velocity was measured as a 10-second average at rest, during occlusion, and immediately following occlusion (peak). The shear stimulus for dilation was calculated as the absolute change in shear rate (SR= 4*velocity/diameter) from occlusion to peak conditions. FMD (% FMD = % change from occlusion to peak diameter) was normalized to the shear stimulus (% FMD/change in SR from occlusion to peak). RESULTS: Effect of age on FMD: Peak SR was lower in older women (361.5 ± 77.2 vs. 530.9 ± 99.5, p<0.05). Normalized FMD was reduced by approximately 50% in older compared to younger women (0.005 ± 0.009 vs. 0.014 ± 0.004, p< 0.05). Effect of age on FMD+CPT: Peak SR remained attenuated in older women (420.9 ±118.2 vs. 654.0 ± 82.1). Normalized FMD still tended to be reduced in older women (0.005 ± 0.005 vs. 0.009 ± 0.003, p=0.08). Interestingly, younger women showed a trend towards a higher shear stimulus (p=0.06) and reduced normalized FMD (p=0.08) during FMD±CPT whereas older women did not (p=0.36 and 0.95, respectively). CONCLUSIONS: In younger women, popliteal artery FMD is blunted during application of an acute sympathetic stimulus due to a reduction in the dilatory response to the shear stimulus. However, administration of an acute sympathetic stimulus during FMD does not appear to significantly attenuate either the shear stimulus or the dilatory response in older women, possibly due to altered adrenergic responsiveness in older adults. This research was supported by an ACSM Foundation Research Grant (FRG) and NIA #T32AG00048.