Department of Molecular & Integrative Physiology, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan.
Brain Res. 2011 Jan 7;1367:181-7. doi: 10.1016/j.brainres.2010.10.013. Epub 2010 Oct 26.
The concentration of calcium in the cerebrospinal fluid (CSF) affects systemic blood pressure; an increase in calcium concentration lowers blood pressure, whereas a decrease raises it. Although this phenomenon has been known for more than 50 years, the precise mechanism is not completely understood. We examined whether the extracellular calcium-sensing receptor (CaSR), which was originally cloned from the parathyroid cells and later found in the brain, contributes to blood pressure regulation by calcium in the CSF. In urethane-anesthetized and artificially ventilated Wistar-Kyoto rats, an intracisternal injection of NPS R-467, an allosteric CaSR activator, decreased blood pressure associated with sympatho-inhibition in a dose-dependent manner. Treatment with an inactivator of the CaSR elicited an increase in blood pressure. Similar results were observed in awake and freely moving animals. In contrast, when the CaSR activator/inactivator was administered into the lateral ventricle, the cardiovascular changes were minimal. These results indicate that the CaSR in the brain contributes, at least in part, to the hypotensive effect of centrally administered calcium and suggests that the CaSR in the lower brainstem participates in tonic regulation of blood pressure by sensing a change in the CSF Ca²+ concentration.
脑脊液（CSF）中钙的浓度会影响全身血压；钙浓度的增加会降低血压，而浓度的降低则会升高血压。尽管这一现象已经为人所知超过 50 年，但确切的机制仍不完全清楚。我们研究了最初从甲状旁腺细胞中克隆出来、后来在大脑中发现的细胞外钙敏感受体（CaSR）是否通过 CSF 中的钙参与血压调节。在乌拉坦麻醉和人工通气的 Wistar-Kyoto 大鼠中，CSF 中脑室内注射全构象 CaSR 激活剂 NPS R-467 可剂量依赖性地降低血压并伴随交感神经抑制。用 CaSR 失活剂处理会引起血压升高。在清醒和自由活动的动物中也观察到类似的结果。相比之下，当 CaSR 激活剂/失活剂被注入侧脑室时，心血管变化很小。这些结果表明，大脑中的 CaSR 至少部分参与了中枢给予钙的降压作用，并提示脑桥下部的 CaSR 通过感知 CSF Ca²+浓度的变化参与血压的紧张性调节。
Zotero 插件