Adenoviral vector demonstrates that angiotensin II-induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat
Adenoviral vector demonstrates that angiotensin II-induced depression of the cardiac baroreflex is mediated by endothelial nitric oxide synthase in the nucleus tractus solitarii of the rat
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DOI：
10.1111/j.1469-7793.2001.0445i.x
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发表时间：
2001-03-01
影响因子：
5.5
通讯作者：
Kasparov, S
中科院分区：
文献类型：
--
作者：
Paton, JFR;Deuchars, J;Kasparov, S
1. 血管紧张素II （ANGII）作用于孤立束核（NTS）的ANGII型1 （AT(1)）受体，可抑制压力反射。由于ANGII刺激一氧化氮（NO）的释放，我们测试了NTS中ANGII介导的压力反射抑制是否依赖于NO的释放。在工作的大鼠NTS心脏-脑干制备（WHBP）中，注射ANGII （500 fmol）或NO供体（500 pmol）均可分别使压力反射增益降低- 56%和- 67% （P < 0.01）。相比之下，虽然ANGII增强了外周化学反射，但NO供体没有作用。NTS微注射非选择性NO合成酶（NOS）抑制剂（L-NAME; 50 pmol）或（L-NMMA; 200 pmol）可防止血管痉挛诱导的压力反射衰减（P < 0.01）。相比之下，神经元特异性NOS抑制剂TRIM （50 pmol）没有效果。利用腺病毒载体，内皮NOS显性阴性突变体（TeNOS）在NTS中双侧表达。TeNOS的表达既不影响基线心血管参数，也不影响气压反射敏感性。然而，将ANGII微注射到转染区域后，对barreflex没有影响。免疫染色显示，enos阳性神经元数量多于标记为AT受体的神经元。同时标记AT(1)受体和eNOS的神经元占enox阳性细胞的23 +/- 5.4%，AT受体阳性细胞的57 +/- 9.2%。内皮细胞也被双重标记为eNOS和AT受体。我们认为，ANGII可以激活位于神经元和/或内皮细胞中的eNOS，从而释放NO，从而选择性地抑制压力反射。
1. Angiotensin II (ANGII) acting on ANGII type 1 (AT(1)) receptors in the solitary tract nucleus (NTS) depresses the baroreflex. Since ANGII stimulates the release of nitric oxide (NO), we tested whether the ANGII-mediated depression of the baroreflex in the NTS depended on NO release.2. In a working heart-brainstem preparation (WHBP) of rat NTS microinjection of either ANGII (500 fmol) or a NO donor (diethylamine nonoate, 500 pmol) both depressed baroreflex gain by -56 and -67 %, respectively (P < 0.01). In contrast, whilst ANGII potentiated the peripheral chemoreflex, the NO donor was without effect.3. NTS microinjection of non-selective NO synthase (NOS) inhibitors (L-NAME; 50 pmol) or (L-NMMA; 200 pmol) prevented the ANGII-induced baroreflex attenuation (P>0.1). In contrast, a neurone-specific NOS inhibitor, TRIM (50 pmol), was without effect.4. Using an adenoviral vector, a dominant negative mutant of endothelial NOS (TeNOS) was expressed bilaterally in the NTS. Expression of TeNOS affected neither baseline cardiovascular parameters nor baroreflex sensitivity. However, ANGII microinjected into the transfected region failed to affect the baroreflex.5. Immunostaining revealed that eNOS-positive neurones were more numerous than those labelled for AT, receptors. Neurones double labelled for both AT(1) receptors and eNOS comprised 23 +/- 5.4% of the eNOX-positive cells and 57 +/- 9.2% of the AT, receptor-positive cells. Endothelial cells were also double labelled for eNOS and AT, receptors.6. We suggest that ANGII activates eNOS located in either neurones and/or endothelial cells to release NO, which acts selectively to depress the baroreflex.