Alpha adrenergic receptor regulation of blood flow during passive leg movement: The impact of age.

Abstract

Passive leg movement (PLM) evokes a robust and transient increase in limb blood flow (LBF). The magnitude of this response is attenuated with aging and this reduction has been largely attributed to diminished nitric oxide (NO) bioavailability. Importantly, aging is also associated with heightened sympathetic activity and altered vasomotor tone, which may contribute to the age‐related reduction in PLM. Therefore, this study sought to determine the contribution of α‐adrenergic signaling to the PLM‐induced LBF response in aging. The central hypothesis is that aging is associated with sympathetically‐mediated restraint of the LBF during PLM. Following intravenous infusion of the β‐blocker propranolol, five young (24±6 yr) and five old (68±4 yr) healthy male subjects underwent PLM during intra‐arterial infusion of saline (CON; control), phenylephrine (PE; α1‐adrenergic receptor agonist) and phentolamine (PHEN; nonspecific α‐adrenergic receptor antagonist). LBF through the common femoral artery was determined second‐by‐second by Doppler ultrasound. Compared with CON, PE did not reduce baseline LBF in the young (CON: 251±11; PE: 193±18 ml/min, p=0.23) or old (CON: 265±18; PE: 239±36 ml/min, p=0.74); however, PHEN increased baseline LBF in both the young (PHEN: 725 ± 63 ml/min, p<0.01 vs. CON) and the old (PHEN: 680 ± 122 ml/min, p<0.01 vs. CON). During PLM in the young, PE reduced the peak change in LBF (ΔPeakLBF) (CON: 595±67; PE: 393±46 ml/min, p=0.038) while PHEN increased the ΔPeakLBF (827 ± 89 ml/min, p=0.02 vs. CON). In contrast, in the old, no changes in ΔPeakLBF in response to PE or PHEN were evident (CON: 342±17; PE: 311±22, PHEN: 378±65 ml/min, p=0.37 for the treatment effect). The magnitude of α‐adrenergic receptor contribution (PHEN ΔPeakLBF – PE ΔPeakLBF) was different between young and old (young: 434±97; old: 67±75 ml/min, p=0.02). The overall hyperemic response, assessed by the LBF area under the curve (LBFAUC) during PLM, was not different when comparing CON (127 ± 23 ml/min) to PE (67 ± 19 ml/min, p=0.22) nor PHEN (210 ± 31 ml/min, p=0.095) in the young; however, LBFAUC was significantly different between PE and PHEN (p=0.02). Neither PE nor PHEN altered the LBFAUC in the old (CON: 82 ± 17, PE: 65 ± 9, PHEN: 127 ± 32 ml/min, p=0.29 for the treatment effect). Although both groups exhibited robust increases in baseline LBF after adrenergic receptor inhibition, only the young demonstrated alterations to the PLM response following stimulation and inhibition of adrenergic receptors. In line with previous findings, we observed sympathetic restraint of resting LBF in both young and old individuals. However, the age related reduction in ΔPeakLBF and LBFAUC during PLM in old individuals does not appear to be associated with augmented sympathetic regulation of vasomotor tone.