Nitric oxide synthase inhibition in healthy adults reduces regional and total cerebral macrovascular blood flow and microvascular perfusion.
Nitric oxide synthase inhibition in healthy adults reduces regional and total cerebral macrovascular blood flow and microvascular perfusion.
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DOI：
10.1113/jp281975
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发表时间：
2021-11
影响因子：
5.5
通讯作者：
Schrage, William G.
中科院分区：
文献类型：
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作者：
Carter, Katrina J.;Ward, Aaron T.;Kellawan, J. Mikhail;Eldridge, Marlowe W.;Al-Subu, Awni;Walker, Benjamin J.;Lee, Jeffrey W.;Wieben, Oliver;Schrage, William G.
一氧化氮（NO）在调节脑血流量（CBF）中的重要性仍未得到解决，部分原因是方法学方法缺乏对全球和区域影响的全面评估。重要的是，NO合成酶（NOS）的表达和活性在大脑前部的一些区域表现得更大，这表明NOS对CBF的影响具有区域特异性。我们假设一氧化氮对健康成人的基础脑血流有贡献，其模式在区域上不同，在前循环中占主导地位。14名健康成人（7名女性，24±5岁）接受了两次磁共振成像（MRI）研究访问，使用生理盐水（安慰剂）或NOS抑制剂L-NMMA，采用随机单盲方法。4D Flow MRI量化了总和区域大血管CBF，而动脉自旋标记（ASL） MRI量化了总和区域微血管灌注。成像前静脉滴注L-NMMA（或容量匹配生理盐水）5分钟。L-NMMA降低了CBF (L-NMMA: 722±100与安慰剂：771±121 mL/min， p = 0.01)，大脑前后循环的相对降低相似（5-7%），部分原因是11条大脑大动脉中9条的横截面积减少。L-NMMA降低了整体微血管灌注（ASL） （L-NMMA: 42±7 mL/100g/min vs.安慰剂：47±8 mL/100g/min， p = 0.02），额叶、顶叶、颞叶和左枕叶的两半球减少了7 - 11%。我们认为一氧化氮有助于大血管和微血管的调节，包括更大的动脉静息直径。与我们的假设相反，一氧化氮对健康年轻人脑灌注的影响在区域上是一致的。EC，内皮细胞；L-arg,精氨酸;L-NMMA NG-monomethyl-L-arginine;NO，一氧化氮；NOS，一氧化氮合酶。一氧化氮有助于维持人类静息时的脑血流。内皮细胞中L-NMMA对一氧化氮合酶的抑制可导致体积流量和局部灌注减少。
The importance of nitric oxide (NO) in regulating cerebral blood flow (CBF) remains unresolved, due in part to methodological approaches, which lack comprehensive assessment of both global and regional effects. Importantly, NO synthase (NOS) expression and activity appear greater in some anterior brain regions, suggesting region-specific NOS influence on CBF. We hypothesized that NO contributes to basal CBF in healthy adults, in a regionally distinct pattern that predominates in the anterior circulation. 14 healthy adults (7 females; 24±5 years) underwent two magnetic resonance imaging (MRI) study visits with saline (placebo) or the NOS inhibitor, L-NMMA, administered in a randomized, single-blind approach. 4D Flow MRI quantified total and regional macrovascular CBF, whereas arterial spin labeling (ASL) MRI quantified total and regional microvascular perfusion. L-NMMA (or volume-matched saline) was infused intravenously for 5 minutes prior to imaging. L-NMMA reduced CBF (L-NMMA: 722±100 vs. placebo: 771±121 mL/min, p = 0.01) with similar relative reductions (5–7%) in anterior and posterior cerebral circulations, due in part to reduced cross sectional area of 9 of 11 large cerebral arteries. Global microvascular perfusion (ASL) was reduced by L-NMMA (L-NMMA: 42±7 vs. placebo: 47±8 mL/100g/min, p = 0.02), with 7–11% reductions in both hemispheres of frontal, parietal, and temporal lobes, and in the left occipital lobe. We conclude NO contributes to macrovascular and microvascular regulation including larger artery resting diameter. Contrary to our hypothesis, the influence of NO on cerebral perfusion appears regionally uniform in healthy young adults. EC, endothelial cell; L-arg, L-arginine; L-NMMA, NG-monomethyl-L-arginine; NO, nitric oxide; NOS, nitric oxide synthase. NO contributes to the maintenance of resting brain blood flow in humans. Inhibition of nitric oxide synthase by L-NMMA in endothelial cells leads to reduced bulk flow and regional perfusion.