Transport of nitrite from large arteries modulates regional blood flow during stress and exercise

J C Muskat; C F Babbs; C J Goergen; V L Rayz

doi:10.3389/fcvm.2023.1146717

Transport of nitrite from large arteries modulates regional blood flow during stress and exercise

Front Cardiovasc Med. 2023 Jun 12:10:1146717. doi: 10.3389/fcvm.2023.1146717. eCollection 2023.

Authors

J C Muskat¹, C F Babbs¹, C J Goergen¹, V L Rayz^{1

2}

Affiliations

¹ Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States.
² Mechanical Engineering, Purdue University, West Lafayette, IN, United States.

Abstract

Background: Acute cardiovascular stress increases systemic wall shear stress (WSS)-a frictional force exerted by the flow of blood on vessel walls-which raises plasma nitrite concentration due to enhanced endothelial nitric oxide synthase (eNOS) activity. Upstream eNOS inhibition modulates distal perfusion, and autonomic stress increases both the consumption and vasodilatory effects of endogenous nitrite. Plasma nitrite maintains vascular homeostasis during exercise and disruption of nitrite bioavailability can lead to intermittent claudication.

Hypothesis: During acute cardiovascular stress or strenuous exercise, we hypothesize enhanced production of nitric oxide (NO) by vascular endothelial cells raises nitrite concentrations in near-wall layers of flowing blood, resulting in cumulative NO concentrations in downstream arterioles sufficient for vasodilation.

Confirmation and implications: Utilizing a multiscale model of nitrite transport in bifurcating arteries, we tested the hypothesis for femoral artery flow under resting and exercised states of cardiovascular stress. Results indicate intravascular transport of nitrite from upstream endothelium could result in vasodilator-active levels of nitrite in downstream resistance vessels. The hypothesis could be confirmed utilizing artery-on-a-chip technology to measure NO production rates directly and help validate numerical model predictions. Further characterization of this mechanism may improve our understanding of symptomatic peripheral artery occlusive disease and exercise physiology.

Keywords: arteriole; autonomic stress; endothelium; nitric oxide; peripheral artery disease; vasodilation; wall shear stress.

Grants and funding

Research reported in this publication was supported in part by the National Institutes of Health under award number R01 HL115267. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.