Predictors of the Pressor Response to the Norepinephrine Transporter Inhibitor, Atomoxetine, in Neurogenic Orthostatic Hypotension.
Predictors of the Pressor Response to the Norepinephrine Transporter Inhibitor, Atomoxetine, in Neurogenic Orthostatic Hypotension.
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DOI：
10.1161/hypertensionaha.119.14483
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发表时间：
2021-08
期刊：
影响因子：
8.3
通讯作者：
Biaggioni, Italo
中科院分区：
文献类型：
--
作者：
Shibao, Cyndya A.;Palma, Jose-Alberto;Celedonio, Jorge E.;Martinez, Jose;Kaufmann, Horacio;Biaggioni, Italo
我们之前报道过去甲肾上腺素转运蛋白抑制剂阿托西汀可以改善神经源性直立性低血压（nOH）患者的站立血压和头晕。本研究的目的是确定阿托西汀加压反应的预测因素。参与临床试验的nOH患者（NCT00223691, NCT1316666）被纳入回顾性分析。所有受试者均接受自主神经功能测试、血浆去甲肾上腺素、收缩压、舒张压（SBP/DBP）和症状评估，分别在坐下和站立时、单剂量阿托西汀18 mg用药前和用药后60分钟。25例患者接受了碘-123标记的甲基碘苄基胍（MIBG）扫描，以估计心脏交感神经去神经的程度。共有99例nOH患者（年龄67±9岁，女性40例）参与研究，其中35例为多系统萎缩，52例为单纯自主神经衰竭，12例为帕金森病。仰卧位血浆去甲肾上腺素水平预测托莫西汀对站立时收缩压（校正R2为0.12,F (3,80) =4.66, p=0.007）和舒张压（校正R2为0.18,F (3,80) =7.04, p=0.001）的影响。托莫西汀治疗后收缩压升高与noh相关症状减少相关（R2=0.14, F (1,44) =8.16, p=0.007）。总之，血浆去甲肾上腺素与nOH患者对阿托西汀的升压反应有一定的相关性。此外，noh相关症状的改善与阿托西汀降压反应的增加有关。
We previously reported that the norepinephrine transporter inhibitor, atomoxetine, improved standing blood pressure and lightheadedness in patients with neurogenic orthostatic hypotension (nOH). The purpose of the present study was to determine the predictors of the pressor response to atomoxetine. Patients with nOH who participated in the clinical trials (NCT00223691, NCT1316666) were included in this retrospective analysis. All subjects underwent autonomic function testing, plasma norepinephrine, systolic, diastolic blood pressure (SBP/DBP) and symptoms assessments, while seated and standing, before and 60 minutes after a single dose of atomoxetine 18 mg. A sub-set of 25 patients underwent iodine-123-labeled metaiodobenzylguanidine (MIBG) scanning to estimate the degree of cardiac sympathetic denervation. A total of 99 subjects with nOH (67±9 years old, 40 women) participated in the study, 35 with multiple system atrophy, 52 with pure autonomic failure and 12 with Parkinson’s Disease. The average orthostatic decrease in their SBP/DBP was −52±26/−22±15 mm Hg. Supine plasma norepinephrine levels predicted the standing SBP (adjusted R2 was 0.12, F (3,80) =4.66, p=0.007) and DBP (adjusted R2 was 0.18, F (3, 80) =7.04, p=0.001) in response to atomoxetine. The increase in SBP after atomoxetine was associated with the decrease in nOH-related symptoms (R2=0.14, F (1,44) =8.16 p=0.007). In conclusion, plasma norepinephrine was modestly associated with the pressor response to atomoxetine in patients with nOH. Additionally, the improvement in nOH-related symptoms was associated with the increase in the pressor response to atomoxetine.