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^G-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_peak and ΔLVC_peak) and area under the curve (LBF_AUC and LVC_AUC). l-NMMA significantly attenuated ΔLBF_peak [492 ± 153 (l-NMMA) vs. 719 ± 238 (control) ml/min], LBF_AUC [57 ± 34 (l NMMA) vs. 147 ± 63 (control) ml], ΔLVC_peak [4.7 ± 1.1 (l-NMMA) vs. 8.0 ± 3.0 (control) ml·min^-1·mmHg^-1], and LVC_AUC [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_peak, r = 0.85 for LBF_AUC, r = 0.94 for ΔLVC_peak, and r = 0.95 for LVC_AUC). 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.

Keywords: blood flow; endothelial function; hemodynamics.

Fig. 1.

Peripheral hemodynamic responses to passive leg movement (PLM) and single PLM (sPLM) performed with and without intra-arterial infusion of N^G-monomethyl-l-arginine (l-NMMA): leg blood flow (LBF) and vascular conductance (LVC). Insets: area under the curve (AUC), calculated as the summed response after normalization for baseline. Values are means ± SE. †Significantly different from control.

Fig. 2.

Absolute peak changes in peripheral hemodynamic responses to passive leg movement (PLM) and single PLM (sPLM) performed with and without intra-arterial infusion of N^G-monomethyl-l-arginine (l-NMMA): peak changes in leg blood flow (ΔLBF_peak) and vascular conductance (ΔLVC_peak). Values are means ± SE. †Significantly different from control.

Fig. 3.

Relationship between peripheral hemodynamic responses and the contribution of nitric oxide (NO) during passive leg movement (PLM) and single PLM (sPLM) performed with and without intra-arterial infusion of N^G-monomethyl-l-arginine (l-NMMA): leg vascular conductance (LVC) peak changes (ΔLVC_peak) and area under the curve (LVC_AUC).

Fig. 4.

Central hemodynamic responses to passive leg movement (PLM) and single PLM (sPLM) performed with and without intra-arterial infusion of N^G-monomethyl-l-arginine (l-NMMA). MAP, mean arterial pressure; CO, cardiac output; SV, stroke volume; HR, heart rate. Values are means ± SE.