Single passive leg movement assessment of vascular function: contribution of nitric oxide

Abstract

Broxterman RM, Trinity JD, Gifford JR, Kwon OS, Kithas AC, Hydren JR, Nelson AD, Morgan DE, Jessop JE, Bledsoe AD, Richardson RS. Single passive leg movement assessment of vascular function: contribution of nitric oxide. J Appl Physiol 123: 1468-1476, 2017. First published August 31, 2017; doi:10.1152/japplphysiol.00533.2017.-The assessment of passive leg movement (PLM)-induced leg blood flow (LBF) and vascular conductance (LVC) is a novel approach to assess vascular function that has recently been simplified to only a single PLM (sPLM), thereby increasing the clinical utility of this technique. As the physiological mechanisms mediating the robust increase in LBF and LVC with sPLM are unknown, we tested the hypothesis that nitric oxide (NO) is a major contributor to the sPLM-induced LBF and LVC response. In nine healthy men, sPLM was performed with and without NO synthase inhibition by intra-arterial infusion of N-monomethyl-l-arginine (l-NMMA). Doppler ultrasound and femoral arterial pressure were used to determine LBF and LVC, which were characterized by the peak change (ΔLBF and ΔLVC) and area under the curve (LBF and LVC). l-NMMA significantly attenuated ΔLBF [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBF [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVC [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min·mmHg], and LVC [0.5 ± 0.3 (l-NMMA) vs. 1.6 ± 0.9 (control) ml/mmHg]. The magnitude of the NO contribution to LBF and LVC was significantly correlated with the magnitude of the control responses ( r = 0.94 for ΔLBF, r = 0.85 for LBF, r = 0.94 for ΔLVC, and r = 0.95 for LVC). These data establish that the sPLM-induced hyperemic and vasodilatory response is predominantly (~65%) NO-mediated. As such, sPLM appears to be a promising, simple, in vivo assessment of NO-mediated vascular function and NO bioavailability. NEW & NOTEWORTHY Passive leg movement (PLM), a novel assessment of vascular function, has been simplified to a single PLM (sPLM), thereby increasing the clinical utility of this technique. However, the role of nitric oxide (NO) in mediating the robust sPLM hemodynamic responses is unknown. This study revealed that sPLM induces a hyperemic and vasodilatory response that is predominantly NO-mediated and, as such, appears to be a promising simple, in vivo, clinical assessment of NO-mediated vascular function and, therefore, NO bioavailability.

The passive leg movement technique for assessing vascular function: defining the distribution of blood flow and the impact of occluding the lower leg

“…This lack of significant differences adds confidence to the current approach of calculating DFA BF in the present investigation. It should also be noted that the current values for baseline CFA and SFA BF are similar to those previously recorded in the literature (Broxterman et al., ; Holland, Brown, Scoutt, & Taylor, ; McDaniel et al., ; Trinity et al., ; Zuj, Prince, Hughson, & Peterson, ).…”

“…Specifically, PLM‐induced hyperaemia is attenuated in ageing and disease, but the effect of cuff occlusion on these results has yet to be determined (Groot et al., ; Trinity et al., ; Witman et al., ). Furthermore, intra‐arterial drug infusion studies, aiming to further quantify the contribution of particular vasodilators to the PLM‐induced hyperaemic response, regularly utilize an occlusion cuff placed just below the knee to localize the effects of a drug to the upper leg (Broxterman et al., ; Trinity et al., ; Trinity et al., ). For instance, Trinity et al.…”

“…Indeed, even though data exist profiling the BF distribution within the major vessels and compartments of the human leg (Chiesa, Trangmar, & González‐Alonso, ; Wray, Uberoi, Lawrenson, & Richardson, ), there has not been an assessment of how this BF distribution is affected by PLM. Interestingly, intra‐arterial drug infusion studies, aiming to further quantify the contribution of particular vasodilators to the PLM‐induced hyperaemic response, utilize an occlusion cuff placed just below the knee to localize the effects of the drug to the upper leg (Broxterman et al., ; Trinity et al., ; Trinity et al., ). However, the impact of such occlusion on the PLM‐induced hyperaemic response remains unknown.…”

The Vascular Side of Chronic Bed Rest: When a Therapeutic Approach Becomes Deleterious

“…Following the blood sample collection, participants were placed in an upright-seated position, near-infrared spectroscopy (NIRS) probes were set on both vastus lateralis and subjects were left at rest in this position for 10 minutes. Subsequently, the single passive leg movement (sPLM) test was performed on one leg, and after 10 minutes rest the test was performed on the other leg [15]. All measurements taken in both right and left limbs were then averaged.…”

“…Recent investigations have revealed that sPLM-induced hyperemia is predominantly a consequence of NO-mediated vasodilation [15]. Therefore, we have adopted this noninvasive and reliable method to determine NO bioavailability [15,16]. During the test, the subjects rested in the upright-seated position for 10 min before the start of data collection and remained in this position throughout this part of the study.…”