Muskat J C, Babbs C F, Goergen C J, Rayz V L
Weldon School of Biomedical Engineering, Purdue University, West Lafayette, IN, United States.
Mechanical Engineering, Purdue University, West Lafayette, IN, United States.
Front Cardiovasc Med. 2023 Jun 12;10:1146717. doi: 10.3389/fcvm.2023.1146717. eCollection 2023.
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.
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.
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.
急性心血管应激会增加全身壁面剪应力（WSS）——血液流动对血管壁施加的摩擦力——由于内皮型一氧化氮合酶（eNOS）活性增强，这会提高血浆亚硝酸盐浓度。上游eNOS抑制可调节远端灌注，自主应激会增加内源性亚硝酸盐的消耗和血管舒张作用。血浆亚硝酸盐在运动过程中维持血管稳态，亚硝酸盐生物利用度的破坏会导致间歇性跛行。
在急性心血管应激或剧烈运动期间，我们假设血管内皮细胞一氧化氮（NO）生成增加会提高流动血液近壁层中的亚硝酸盐浓度，导致下游小动脉中的NO浓度累积到足以实现血管舒张的水平。
利用分叉动脉中亚硝酸盐运输的多尺度模型，我们测试了在心血管应激的静息和运动状态下股动脉血流的这一假设。结果表明，亚硝酸盐从上游内皮的血管内运输可导致下游阻力血管中亚硝酸盐达到血管舒张活性水平。利用芯片动脉技术直接测量NO生成速率可证实这一假设，并有助于验证数值模型预测。对该机制的进一步表征可能会增进我们对症状性外周动脉闭塞性疾病和运动生理学的理解。
