ANGIOTENSIN RECEPTOR FUNCTION IN THE DORSAL MEDULLA

其目标是扩展最新的发现，与各种 传送器(RR)，以确定是否直接或间接作用于 血管紧张素肽介导急性心血管反应和压力感受器效应。 初步数据表明，血管紧张素II增加了物质的基础释放 P(SP)，但有减少高钾引起的SP释放的趋势。 另外，也有研究表明血管紧张素Ⅱ引起结状神经节兴奋。 神经元，在此之后存在部分去极化。这将倾向于 以降低对后续刺激的反应性。在此基础上，我的新 假设血管紧张素转换酶II释放SP或去甲肾上腺素(NE)。 突触细胞介导急性降压和心动过缓的作用。 然而，Ang II抑制(或不促进)迷走神经释放SP 当压力感受器反射被激活时，传入纤维导致 压力感受器反射的衰减。目标一是完成 DMM中血管紧张素Ⅱ结合部位的药理学研究 血管紧张素-血管紧张素受体亚型(S)介导的SP、NE和 使用亚型选择性拮抗剂从DMM切片中提取前列腺素(PG)。 这些研究是基于我们发现的地形分布 对AT1和AT2竞争对手具有差异敏感性的DMM受体。 目的II确定血管紧张素转换酶多肽是否具有剂量相关的心血管效应 与SP、NE或PG的释放有关。局部注射 相对特异的神经毒素和药理拮抗剂 以上的RR和突触阻断将被用来评估是否 阻断将改变微量注射血管紧张素转换酶的急性心血管反应 DMM中的多肽。而血管紧张素转换酶多肽的急性心血管效应 DMM似乎模拟反射的激活(低血压和 心动过缓)，Ang II外周或中枢输注抑制 压力感受器反射。血管紧张素转换酶II和血管紧张素-(1-7)的差异释放 P物质、去甲肾上腺素和前列腺素，对反射有相反的作用。因此， 血管紧张素Ⅱ与血管紧张素-(1-7)对压力感受器反射的相反作用 是对SP、NE和PGs释放的不同影响的结果。 目标三将确定是否封锁或耗尽上述树 系统改变由血管紧张素转换成的反射的调制。 激活前和激活过程中的平行微透析实验 反射将验证特定TRs的释放是由 ANG多肽的作用方式与预期的效果一致 条件反射。

The objectives are to extend recent findings of interactions with various transmitters (TRs) to determine whether direct or indirect actions of angiotensin peptides mediate the acute CV and baroreceptor effects. Preliminary data suggest that Ang II increases basal release of substance P (SP), but tends to reduce SP release evoked by high potassium. Moreover, others showed that Ang II causes excitation of nodose ganglion neurons, after which a partial depolarization exists. This would tend to reduce responsiveness to a subsequent stimulus. On this basis, my new hypothesis is that Ang II releases SP or norepinephrine (NE) from post- synaptic cells to mediate the acute hypotensive and bradycardic effects. However, Ang II inhibits (or does not facilitate) SP release from vagal afferent fibers when the baroreceptor reflex is activated, leading to attenuation of the baroreceptor reflex. AIM I is to complete the pharmacological profile of the Ang II binding sites in the DMM by determining the Ang receptor subtype(s) mediating release of SP, NE and prostaglandins (PGs) from DMM slices using subtype selective antagonists. These studies are based on our finding of a topographic distribution of DMM receptors with differential sensitivity to AT1 and AT2 competitors. AIM II is to determine whether dose-related CV effects of Ang peptides are linked to release of SP, NE or PGs. Localized injections of relatively specific neurotoxins and pharmacologic antagonists for the above TRs, and synaptic blockade will be used to assess whether the blockade will alter the acute CV responses to microinjections of Ang peptides in the DMM. While the acute CV effects of Ang peptides in the DMM appear to mimic activation of the reflex (hypotensive and bradycardic), Ang II infusions peripherally or centrally inhibit the baroreceptor reflex. Ang II and Ang-(1-7) differentially alter release of SP, NE and PGs, and have opposite effects on the reflex. Thus the opposite effects of Ang II versus Ang-(1-7) on the baroreceptor reflex are a consequence of differential effects on SP, NE, and PGs release. AIM III will determine whether blockade or depletion of the above TR systems alters modulation of the reflex resulting from the Ang peptides. Parallel microdialysis experiments before and during activation of the reflex will verify that release of the particular TRs is modulated by the Ang peptides in a manner consistent with the predicted effects on the reflex.