The role of nitric oxide in passive leg movement‐induced vasodilatation with age: insight from alterations in femoral perfusion pressure

Abstract

Key pointsr The passive leg movement (PLM) model is a novel approach to assess vascular function. r 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.r 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.r 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.Abstract 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 ( LVC peak ) 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 LVC peak 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 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.

Passive leg movement-induced vasodilation in women: the impact of age

“…This PLM-induced hyperemia has previously been reported in both young and old men; however, the magnitude of the vasodilatory response to PLM is significantly attenuated with age (11,23). Recent investigations into the mechanisms responsible for the PLM response conclude that PLM-induced vasodilation is predominantly NO mediated in young men, as evidenced by an ϳ80 -90% reduction in the hyperemic response during intraarterial infusion of the NO synthase (NOS) inhibitor N Gmonomethyl-L-argenine (10,28,39). Furthermore, by once again using NOS inhibition, both Trinity et al (38) and Groot et al (10) reported that the attenuated PLM-induced vasodilation described in older men was a consequence of reduced NO bioavailability with age.…”

“…2). Additionally, the rapid vasodilatory response (slope of the increasing LVC over time for the first 9 s) to PLM, previously determined to be NO-independent in men in the supine posture (10,38), was also significantly attenuated with age in women (ϳ 70%; Fig. 4).…”

“…In the supine posture, PLM initiates a vasodilatory response in young men that has been documented to be attenuated in old men (28,39), is predominantly nitric oxide (NO) mediated, and therefore likely reflects endothelium-dependent vascular function (28,39). Interestingly, when femoral perfusion pressure (FPP) is increased by moving from the supine to the uprightseated posture, young men exhibit an NO-mediated vasodilatory reserve capacity, whereas old men, due to diminished NO bioavailability, do not (10,11). Likewise, the initial vasodilatory response to PLM (ϳ9 s) differs between young and old men, with the old demonstrating a slower onset (10,11,38).…”

“…Recent investigations into the mechanisms responsible for the PLM response conclude that PLM-induced vasodilation is predominantly NO mediated in young men, as evidenced by an ϳ80 -90% reduction in the hyperemic response during intraarterial infusion of the NO synthase (NOS) inhibitor N Gmonomethyl-L-argenine (10,28,39). Furthermore, by once again using NOS inhibition, both Trinity et al (38) and Groot et al (10) reported that the attenuated PLM-induced vasodilation described in older men was a consequence of reduced NO bioavailability with age. However, before this investigation, the PLM model had not been used to examine alterations in vascular function with age in women.…”

“…Interestingly, when femoral perfusion pressure (FPP) is increased by moving from the supine to the uprightseated posture, young men exhibit an NO-mediated vasodilatory reserve capacity, whereas old men, due to diminished NO bioavailability, do not (10, 11). Likewise, the initial vasodilatory response to PLM (ϳ9 s) differs between young and old men, with the old demonstrating a slower onset (10,11,38). Due to the powerful antiatherogenic properties of NO (18,34), and the importance of intact vascular function in cardiovascular disease (CVD) prevention, an assessment such as the response to PLM, which has the potential to be used across the life span, may be of great clinical importance.…”