Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness.
Endothelial cell-specific aryl hydrocarbon receptor knockout mice exhibit hypotension mediated, in part, by an attenuated angiotensin II responsiveness.
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DOI：
10.1016/j.bcp.2011.06.011
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发表时间：
2011-09-01
影响因子：
5.8
通讯作者：
Walker MK
中科院分区：
文献类型：
--
作者：
Agbor LN;Elased KM;Walker MK
芳烃受体敲除小鼠（ahr−/−）的低血压部分是由血管紧张素（Ang）II对基础血压（BP）的贡献减少介导的。由于AHR在内皮细胞（EC）中高度表达，我们假设EC特异性ahr−/−（ECahr−/−）小鼠将表现出相似的表型。我们通过将AHR floxed小鼠（ahrfx/fx）与表达由EC特异性启动子驱动的Cre重组酶的小鼠杂交来产生ECahr−/−小鼠。在急性注射血管紧张素II或长期使用血管紧张素转换酶抑制剂（ACEi）治疗之前和之后，通过无线电遥测术评估血压。ECahr−/−小鼠表现出水肿（ECahr+/+：116.1 ± 1.4; ECahr−/−：107.4 ± 2.0 mmHg，n=11，p<0.05），并对Ang II和ACEi表现出显著不同的反应。虽然Ang II增加了两种基因型的血压，但ECahr+/+小鼠的血压持续增加，而ECahr−/−小鼠的血压稳步下降。曲线下面积分析显示，ECahr−/−小鼠在30分钟内Ang II诱导的舒张压（DBP）升高显著较低（ECahr+/+ 1297 ± 223 mmHg/30 min; ECahr−/−AUC：504 ± 138 mmHg/30 min，p<0.05）。相比之下，虽然ACEi降低了两种基因型的血压，但在ECahr−/−小鼠中，治疗后DBP的随后升高显著延迟。ECahr−/−小鼠还表现出血管和脂肪Ang II 1型受体（AT 1 R）表达减少，以及血管脂肪存在时主动脉Ang II依赖性血管收缩减少。总之，这些数据表明，ECahr−/−小鼠的低血压是由于血管对Ang II的反应性降低所致，而血管对Ang II的反应性受AT 1 R表达和脂肪的影响。
Hypotension in aryl hydrocarbon receptor knockout mice (ahr−/−) is mediated, in part, by a reduced contribution of angiotensin (Ang) II to basal blood pressure (BP). Since AHR is highly expressed in endothelial cells (EC), we hypothesized that EC-specific ahr−/− (ECahr−/−) mice would exhibit a similar phenotype. We generated ECahr−/− mice by crossing AHR floxed mice (ahrfx/fx) to mice expressing Cre recombinase driven by an EC-specific promoter. BP was assessed by radiotelemetry prior to and following an acute injection of Ang II or chronic treatment with an angiotensin converting enzyme inhibitor (ACEi). ECahr−/− mice were hypotensive (ECahr+/+: 116.1 ± 1.4; ECahr−/−: 107.4 ± 2.0 mmHg, n=11, p<0.05) and exhibited significantly different responses to Ang II and ACEi. While Ang II increased BP in both genotypes, the increase was sustained in ECahr+/+, whereas the increase in ECahr−/− mice steadily declined. Area under the curve analysis showed that Ang II-induced increase in diastolic BP (DBP) over 30 min was significantly lower in ECahr−/− mice (ECahr+/+ 1297 ± 223 mmHg/30 min; ECahr−/−AUC: 504 ± 138 mmHg/30 min, p<0.05). In contrast, while ACEi decreased BP in both genotypes, the subsequent rise in DBP after treatment was significantly delayed in the ECahr−/− mice. ECahr−/− mice also exhibited reduced vascular and adipose Ang II type 1 receptor (AT1R) expression, and reduced aortic Ang II-dependent vasoconstriction in the presence of vascular adipose. Taken together these data suggest that hypotension in ECahr−/− mice results from reduced vascular responsiveness to Ang II that is influenced by AT1R expression and adipose.
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影响因子：
8.3
作者：
Lund, Amie K.;Agbor, Larry N.;Walker, Mary K.
通讯作者：
Walker, Mary K.
影响因子：
4.9
作者：
Giacchetti, G;Sechi, LA;Schambelan, M
通讯作者：
Schambelan, M
影响因子：
10.8
作者：
Han, Zhiyi;Miwa, Yoshikazu;Sasaguri, Toshiyuki
通讯作者：
Sasaguri, Toshiyuki
DOI：
10.1073/pnas.190256997
发表时间：
2000-09-12
影响因子：
11.1
作者：
Lahvis, GP;Lindell, SL;Bradfield, CA
通讯作者：
Bradfield, CA
影响因子：
3.9
作者：
Hankinson, O
通讯作者：
Hankinson, O