Hyperosmotic activation of CNS sympathetic drive: implications for cardiovascular disease.
Hyperosmotic activation of CNS sympathetic drive: implications for cardiovascular disease.
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中枢神经系统交感神经驱动的高渗激活：对心血管疾病的影响。
DOI：
10.1113/jphysiol.2010.191940
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发表时间：
2010
期刊：
影响因子：
--
通讯作者：
Stocker,SeanD
中科院分区：
文献类型：
--
作者：
Toney,GlennM;Stocker,SeanD
现在的证据表明，过度的交感神经活动（SNA）会显着导致盐敏感的心血管疾病。尽管在各种心血管疾病模型中支持 SNA 升高的 CNS 机制已得到深入研究，但许多机制细节仍然未知。近年来的研究表明，体液渗透压的急性和慢性增加都会导致SNA升高。这些发现提出了盐敏感性心血管疾病可能至少部分由中枢神经系统交感神经驱动的直接渗透感觉激活引起的可能性。在这篇简短的综述中，我们强调了包括我们自己的实验室在内的多个实验室的最新发现，这些发现表明，前脑器官终板血管器 (OVLT) 的神经元通过招募下丘脑、脑干和脊髓特定区域的神经元，在触发 SNA 高渗激活中发挥着关键作用。尽管 OVLT 神经元本质上具有渗透敏感性，并且在暴露于细胞外高渗性时会收缩，但尚不清楚这些过程是否在功能上相关。尽管 OVLT 神经元的急性高渗激活主要依赖于 TRPV1 通道，但 TRPV1−/− 小鼠的研究表明，急性和长期的渗透压调节反应在很大程度上保持完整。因此，OVLT 神经元的急性和慢性渗透感觉转导可能是通过不同的机制介导的。我们推测牛磺酸等有机渗透剂以及细胞外酸化等可能的新过程可能有助于 OVLT 神经元的长期渗透感觉转导，因此可能参与盐敏感心血管疾病中 SNA 的升高。
Evidence now indicates that exaggerated sympathetic nerve activity (SNA) significantly contributes to salt‐sensitive cardiovascular diseases. Although CNS mechanisms that support the elevation of SNA in various cardiovascular disease models have been intensively studied, many mechanistic details remain unknown. In recent years, studies have shown that SNA can rise as a result of both acute and chronic increases of body fluid osmolality. These findings have raised the possibility that salt‐sensitive cardiovascular diseases could result, at least in part, from direct osmosensory activation of CNS sympathetic drive. In this brief review we emphasize recent findings from several laboratories, including our own, which demonstrate that neurons of the forebrain organum vasculosum laminae terminalis (OVLT) play a pivotal role in triggering hyperosmotic activation of SNA by recruiting neurons in specific regions of the hypothalamus, brainstem and spinal cord. Although OVLT neurons are intrinsically osmosensitive and shrink when exposed to extracellular hypertonicity, it is not yet clear if these processes are functionally linked. Whereas acute hypertonic activation of OVLT neurons critically depends onTRPV1channels, studies inTRPV1−/−mice suggest that acute and long‐term osmoregulatory responses remain largely intact. Therefore, acute and chronic osmosensory transduction by OVLT neurons may be mediated by distinct mechanisms. We speculate that organic osmolytes such as taurine and possibly novel processes such as extracellular acidification could contribute to long‐term osmosensory transduction by OVLT neurons and might therefore participate in the elevation of SNA in salt‐sensitive cardiovascular diseases.