β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism.
β2-adrenergic stress evaluation of coronary endothelial-dependent vasodilator function in mice using (11)C-acetate micro-PET imaging of myocardial blood flow and oxidative metabolism.
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DOI：
10.1186/s13550-014-0068-9
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发表时间：
2014-12
期刊：
影响因子：
3.2
通讯作者：
deKemp RA
中科院分区：
文献类型：
--
作者：
Croteau E;Renaud JM;Archer C;Klein R;DaSilva JN;Ruddy TD;Beanlands RS;deKemp RA
内皮功能障碍与血管危险因素如血脂异常、高血压和糖尿病相关，导致冠状动脉粥样硬化。使用冷加压试验（CPT）的交感神经应激已被用于通过正电子发射断层扫描（PET）心肌血流（MBF）成像来测量人类的冠状动脉内皮功能，但在小动物模型中并不实用。本研究采用[11 C]醋酸盐micro-PET测量一氧化氮介导的内皮血流储备（EFRNOM）（肾上腺素能应激/静息MBF）和心肌耗氧量（MVO 2），使用沙丁胺醇β2-肾上腺素能激活来表征小鼠的冠状动脉血管功能。在静息+沙丁胺醇（SB 0.2，1.0 μg/kg/min）和去甲肾上腺素（NE 3.2 μg/kg/min）应激下进行[11 C]乙酸PET MBF，以测量MBF反应指数。用α-肾上腺素能拮抗剂酚妥拉明（PHE）预处理评价NE的β-肾上腺素能特异性，用SB评价NE的β2-选择性。用小剂量SB和NE对正常小鼠进行调整心率×收缩压乘积（RPP）的变化，测得相同的负荷/静息MBF比值为1.4（相当于人CPT反应）。MBF反应与MVO 2的变化相关（p = 0.02）。使用一氧化氮合酶（NOS）抑制小鼠（NG-硝基-L-精氨酸甲酯（L-NAME）预处理和内皮一氧化氮合酶（eNOS）敲除）来评估EFRNOM，其中低剂量SB-和NE-应激MBF反应被完全阻断（p = 0.02）。在高剂量SB应激下，NOS抑制后MBF比率降低0.4（p = 0.03）。低剂量沙丁胺醇β2-肾上腺素能应激[11 C]醋酸酯micro-PET成像可用于测量小鼠冠状动脉特异性EFRNOM，并可能适用于评估小动物疾病模型中的内皮功能障碍和评估新疗法。本文的在线版本（doi：10.1186/s13550-014-0068-9）包含补充材料，可供授权用户使用。
Endothelial dysfunction is associated with vascular risk factors such as dyslipidemia, hypertension, and diabetes, leading to coronary atherosclerosis. Sympathetic stress using cold-pressor testing (CPT) has been used to measure coronary endothelial function in humans with positron emission tomography (PET) myocardial blood flow (MBF) imaging, but is not practical in small animal models. This study characterized coronary vasomotor function in mice with [11C]acetate micro-PET measurements of nitric-oxide-mediated endothelial flow reserve (EFRNOM) (adrenergic-stress/rest MBF) and myocardial oxygen consumption (MVO2) using salbutamol β2-adrenergic-activation. [11C]acetate PET MBF was performed at rest + salbutamol (SB 0.2, 1.0 μg/kg/min) and norepinephrine (NE 3.2 μg/kg/min) stress to measure an index of MBF response. β-adrenergic specificity of NE was evaluated by pretreatment with α-adrenergic-antagonist phentolamine (PHE), and β2-selectivity was assessed using SB. Adjusting for changes in heart rate × systolic blood pressure product (RPP), the same stress/rest MBF ratio of 1.4 was measured using low-dose SB and NE in normal mice (equivalent to human CPT response). The MBF response was correlated with changes in MVO2 (p = 0.02). Nitric oxide synthase (NOS)-inhibited mice (Ng-nitro-L-arginine methyl ester (L-NAME) pretreatment and endothelial nitric oxide synthase (eNOS) knockout) were used to assess the EFRNOM, in which the low-dose SB- and NE-stress MBF responses were completely blocked (p = 0.02). With high-dose SB-stress, the MBF ratio was reduced by 0.4 following NOS inhibition (p = 0.03). Low-dose salbutamol β2-adrenergic-stress [11C]acetate micro-PET imaging can be used to measure coronary-specific EFRNOM in mice and may be suitable for assessment of endothelial dysfunction in small animal models of disease and evaluation of new therapies. The online version of this article (doi:10.1186/s13550-014-0068-9) contains supplementary material, which is available to authorized users.
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DOI：
10.1046/j.1540-8167.2004.03105.x
发表时间：
2004-03-01
影响因子：
2.7
作者：
Insulander, P;Juhlin-Dannfelt, A;Vallin, H
通讯作者：
Vallin, H
影响因子：
5.5
作者：
Monahan, Kevin D.;Feehan, Robert P.;Gao, Zhaohui
通讯作者：
Gao, Zhaohui
DOI：
10.1152/ajpheart.00419.2002
发表时间：
2003-02-01
影响因子：
4.8
作者：
Okajima, M;Takamura, M;Lavallée, M
通讯作者：
Lavallée, M
影响因子：
2.4
作者：
Klein, Ran;Renaud, Jennifer M.;deKemp, Robert A.
通讯作者：
deKemp, Robert A.
DOI：
10.1016/j.pathophys.2008.02.002
发表时间：
2008-06-01
期刊：
Pathophysiology : the official journal of the International Society for Pathophysiology
影响因子：
--
作者：
Khazaei, M;Moien-Afshari, F;Laher, I
通讯作者：
Laher, I