Passive leg movement and nitric oxide-mediated vascular function: the impact of age

Abstract

In young healthy men, passive leg movement (PLM) elicits a robust nitric oxide (NO)-dependent increase in leg blood flow (LBF), thus providing a novel approach to assess NO-mediated vascular function. While the magnitude of the LBF response to PLM is markedly reduced with age, the role of NO in this attenuated response in the elderly is unknown. Therefore, this study sought to determine the contribution of NO in the PLM-induced LBF with age. Fourteen male subjects (7 young, 24 ± 1 yr; and 7 old, 75 ± 3 yr) underwent PLM with and without NO synthase (NOS) inhibition achieved by intra-arterial infusion of N(G)-monomethyl-L-arginine (L-NMMA). LBF was determined second-by-second by Doppler ultrasound, and central hemodynamics were measured by finger photoplethysmography. NOS inhibition blunted the PLM-induced peak increase in LBF in the young (control: 668 ± 106;

L-nmma: 431 ± 95 Δml/min; P = 0.03) but had no effect in the old (control: 266 ± 98;

L-nmma: 251 ± 92 Δml/min; P = 0.59). Likewise, the magnitude of the reduction in the overall (i.e., area under the curve) PLM-induced LBF response to NOS inhibition was less in the old (LBF: -31 ± 18 ml) than the young (LBF: -129 ± 21 ml; P < 0.01). These findings suggest that the age-associated reduction in PLM-induced LBF in the elderly is primarily due to a reduced contribution to vasodilation from NO and therefore support the use of PLM as a novel approach to assess NO-mediated vascular function across the lifespan.

Keywords: aging; endothelial function; flow-mediated dilation; leg blood flow; nitric oxide.

Figures

Fig. 1.

Passive limb movement (PLM)-induced hyperemia in young and old with and without intra-arterial NG-monomethyl-l-arginine (l-NMMA) infusion. A: absolute leg blood flow (LBF; ml/min). B: change in LBF, normalized for the resting reduction in LBF due to l-NMMA. C: LBF area under the curve (AUC) calculated as the summed second-by-second response during the first 60 s of movement. Values are means ± SE. To increase clarity of the data presented, only the first 60 s of PLM are displayed. One minute of baseline data was collected before PLM occurred. *P < 0.05, significant difference between control and l-NMMA.

Fig. 2.

PLM-induced vasodilatory response in young and old with and without intra-arterial l-NMMA infusion. A: leg vascular conductance (LVC) AUC calculated as the summed second-by-second response during the first 60 s of movement. B: l-NMMA-induced reduction in LVC AUC. Values are means ± SE. *P < 0.05, significant difference between control and l-NMMA. †P < 0.05, significant difference between young and old. #P < 0.05, significant reduction due to l-NMMA.

Fig. 3.

Change in LBF in the nonmoved limb during PLM in young and old with and without intra-arterial l-NMMA infusion. Significant main effect of interaction for the young (trial × time). One minute of baseline data was collected before PLM. To increase clarity of the data presented, only the first 60 s of PLM are displayed. Values are means ± SE.

Fig. 4.

PLM-induced changes in mean arterial pressure in young and old with and without intra-arterial l-NMMA infusion. Absolute mean arterial pressure (MAP; mmHg; A) and MAP AUC (B) calculated as the summed second-by-second response during the first 60 s of movement. Values are means ± SE. *P < 0.05, significant difference between control and l-NMMA.