Effects of Acute Nitric Oxide Synthase Inhibition on Lower Leg Vascular Function in Chronic Tetraplegia

Abstract

Background/Objective: To improve our understanding of the lower-leg vascular responses of nitric oxide synthase inhibition in persons with tetraplegia. Participants: Six people with chronic tetraplegia and 6 age-matched controls. Methods: Lower-leg relative vascular resistance and venous volume variation were obtained by venous occlusion plethysmography and blood pressure by auscultation at baseline. Postintravenous infusion of the nitric oxide synthase inhibitor N G -nitro-L-arginine-methyl-ester (1 mg?kg 21) or placebo on separate days. Results: At baseline in the group with tetraplegia compared with controls, mean arterial pressure and relative vascular resistance of the leg were significantly lower. After nitric oxide synthase inhibition, mean arterial pressure and lower leg vascular resistance were significantly elevated in both groups. There were no group or intervention differences in venous volume variation. Conclusion: These preliminary results suggest that nitric oxide synthase inhibition with 1 mg?kg 21 N G -nitro-L-arginine-methyl-ester normalizes seated blood pressure and lower leg vascular resistance to control group baseline levels.

Systemic Blockage of Nitric Oxide Synthase by L-NAME Increases Left Ventricular Systolic Pressure, Which Is Not Augmented Further by Intralipid®

“…Taken together with findings of previous studies, the inability of Intralipid ® to induce an increase in LVSP after L-NAME pretreatment (Fig. 5A and 6A) appears to be associated with Intralipid ® -mediated nitric oxide inhibition 27-29. This Intralipid ® -mediated nitric oxide inhibition seems to be one of the putative underlying mechanisms responsible for Intralipid ® -induced LSVP increase and may contribute to the increased systemic vascular resistance, decreased flow-mediated nitric oxide-dependent vasodilation, and decreased arterial compliance observed during intravenous infusion of Intralipid ® in previous in vivo studies 15,16.…”

“…In addition, in human umbilical vein endothelial cells, Lipofundin ® MCT/LCT and Intralipid ® increase production of oxidized dichlorofluorescein, which is considered an indicator of reactive oxygen species 11 . Acute administration of the non-specific NOS inhibitor L-NAME causes hypertension and increased vascular resistance through inhibition of endothelial nitric oxide release 27 - 29 . Taken together with findings of previous studies, the inability of Intralipid ® to induce an increase in LVSP after L-NAME pretreatment (Fig.…”

Cutaneous microvascular perfusion responses to insulin iontophoresis are differentially affected by insulin resistance after spinal cord injury

“…compensatory reduction to cross-sectional area of the arterial tree with lean tissue atrophy) and its contribution to endothelial dysfunction (Boot et al 2002;Olive et al 2003;de Groot et al 2004de Groot et al , 2005de Groot et al , 2006Bleeker et al 2005;Thijssen et al 2005Thijssen et al , 2008Totosy de Zepetnek et al 2015a,b). There is no evidence to suggest that the endothelial dysfunction observed in these reports was a consequence of reduced nitric oxide bioavailability, but instead it is speculated to be a reflection of endothelial responsiveness to the presence of nitric oxide, which upon inhibition has been demonstrated to result in marked increases in peripheral vascular resistance (La Fountaine et al 2009). The presence of microvascular endothelial dysfunction is associated with an increased risk for cardiovascular-related disease, which has been reported as one of the primary causes of death after the first post-injury year (DeVivo et al 1992;Garshick et al 2005;Wahman et al 2010;Chen et al 2013;Cragg et al 2013).…”

“…There is no evidence to suggest that the endothelial dysfunction observed in these reports was a consequence of reduced nitric oxide bioavailability, but instead it is speculated to be a reflection of endothelial responsiveness to the presence of nitric oxide, which upon inhibition has been demonstrated to result in marked increases in peripheral vascular resistance (La Fountaine et al . ). The presence of microvascular endothelial dysfunction is associated with an increased risk for cardiovascular‐related disease, which has been reported as one of the primary causes of death after the first post‐injury year (DeVivo et al .…”

Application of a Nitric Oxide Sensor in Biomedicine

“…Application of an eNOS inhibitor on the venous network normalizes venous vascular resistance and blood pressure values in the lower limbs, although these results are still preliminary [ 79 ].…”