AT(1) antisense distinguishes receptors mediating angiotensin II actions in solitary tract nucleus.
AT(1) antisense distinguishes receptors mediating angiotensin II actions in solitary tract nucleus.
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AT(1) 反义区分孤束核中介导血管紧张素 II 作用的受体。
DOI：
10.1161/01.hyp.37.5.1292
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
Averill,DB
中科院分区：
文献类型：
--
作者：
Diz,DI;Westwood,B;Averill,DB
—孤束核 (nTS) 中的血管紧张素 (Ang) II 受体位于迷走神经感觉传入纤维末端以及神经元细胞体上。体外切片制备结果表明，Ang II 约 50% 的神经元兴奋作用来自突触前受体的作用。纤维末端与神经元细胞胞体的作用对 nTS 中 Ang II 的心血管作用的不同贡献尚不清楚。我们使用了 1 型血管紧张素 (AT1) 受体的反义寡核苷酸，这应该减少注射部位神经元上的受体，但不会减少投射到 nTS 的纤维末端上的受体。在用氯醛糖/尿烷麻醉的雄性 Sprague-Dawley 大鼠中，向 nTS 中注射 Ang II (250 fmol/30 nL) 可使血压降低 14±1 mm Hg，心率降低 13±1 bpm (n=8)。 尽管将 AT1 反义 (164 pmol/120 nL) 注射到 nTS 后 90 分钟和 150 分钟，Ang II 诱导的压力仍然显着下降，但反应减弱了 50% (P<0.01)。心率反应在 150 分钟时间点被完全阻断。乱序序列寡核苷酸在任何时候都不会改变 Ang II 反应。当 nTS 的反义注射侧和未注射侧与受体放射自显影相比较时，125I[Sar1Thr8]-Ang II 结合减少了 40%。这一发现与传入纤维上持续存在 AT1 受体一致。这种独特的策略表明，突触前纤维末端和 nTS 神经元都参与 Ang II 的降血压作用，而心率反应很大程度上是由于直接作用于 nTS 神经元和迷走神经传出通路的激活。
—Angiotensin (Ang) II receptors in the solitary tract nucleus (nTS) are located on vagal sensory-afferent fiber terminals as well as on neuronal cell bodies. Results from in vitro slice preparations indicate that ≈50% of the neuronal excitatory actions of Ang II result from actions at presynaptic receptors. The differential contribution of actions on fiber terminals versus neuronal cell soma to the cardiovascular effects of Ang II in the nTS is not known. We used antisense oligonucleotides to the angiotensin type 1 (AT1) receptor, which should reduce receptors on neurons within the injection site but not those on fiber terminals projecting to the nTS. Ang II injections (250 fmol/30 nL) into the nTS reduced blood pressure by 14±1 mm Hg and heart rate by 13±1 bpm (n=8) in male Sprague-Dawley rats anesthetized with chloralose/urethane. Although there was still a significant fall in pressure that was induced by Ang II at 90 and 150 minutes after AT1antisense (164 pmol/120 nL) was injected into the nTS, the response was blunted 50% (P<0.01). Heart rate responses were completely blocked at the 150-minute time point. Scrambled sequence oligonucleotides did not alter Ang II responses at any time. There was a 40% reduction in125I[Sar1Thr8]-Ang II binding when antisense-injected and noninjected sides of the nTS were compared with receptor autoradiography. This finding is consistent with the continued presence of AT1receptors on afferent fibers. This unique strategy illustrates that both presynaptic fiber terminals and nTS neurons are involved in the blood pressure lowering actions of Ang II, whereas heart rate responses are largely due to actions directly on nTS neurons and activation of vagal efferent pathways.