PDF(Pubmed)
Abstract：
Stimulation of the calcium-sensing receptor (CaSR) regulates vascular contractility, but cellular mechanisms involved remain unclear. This study investigated the role of perivascular sensory nerves in CaSR-induced relaxations of male rat mesenteric arteries. In fluorescence studies, colocalisation between synaptophysin, a synaptic vesicle marker, and the CaSR was present in the adventitial layer of arterial segments. Using wire myography, increasing external Ca2+ concentration ([Ca2+]o) from 1 to 10 mM induced vasorelaxations, previously shown to involve the CaSR, which were inhibited by pretreatment with capsaicin. [Ca2+]o-induced vasorelaxations were partially reduced by the calcitonin gene-related peptide (CGRP) receptor blockers, CGRP 8-37 and BIBN 4096, and the neurokinin 1 (NK1) receptor blocker L733,060. The inhibitory effect of CGRP 8-37 required a functional endothelium whereas the inhibitory action of L733,060 did not. Complete inhibition of [Ca2+]o-induced vasorelaxations occurred when CGRP 8-37 and L733,060 were applied together. [Ca2+]o-induced vasorelaxations in the presence of capsaicin were abolished by the ATP-dependent K+ channel (KATP) blocker PNU 37883, but unaffected by the endothelium nitric oxide synthase (eNOS) inhibitor L-NAME. We suggest that the CaSR on perivascular sensory nerves mediate relaxations in rat mesenteric arteries via endothelium-dependent and -independent mechanisms involving CGRP and NK1 receptor-activated NO production and KATP channels, respectively.
摘要：
钙敏感受体（CaSR）的刺激调节血管收缩，但所涉及的细胞机制仍不清楚。这项研究调查了血管周围感觉神经在CaSR诱导的雄性大鼠肠系膜动脉舒张中的作用。在荧光研究中，突触素之间的共定位，突触小泡标记物,CaSR存在于动脉段的外膜层中。使用导线肌电图,增加外部Ca2+浓度（[Ca2+]o）从1到10mM诱导的血管舒张，先前显示涉及CaSR，被辣椒素预处理抑制。降钙素基因相关肽（CGRP）受体阻滞剂部分减少了[Ca2]o诱导的血管舒张，CGRP8-37和BIBN4096，以及神经激肽1（NK1）受体阻断剂L733,060。CGRP8-37的抑制作用需要功能性内皮，而L733,060的抑制作用则没有。当CGRP8-37和L733,060一起应用时,发生[Ca2+]o诱导的血管舒张的完全抑制。ATP依赖性K通道（KATP）阻断剂PNU37883消除了辣椒素存在下[Ca2]o诱导的血管舒张，但不受内皮一氧化氮合酶（eNOS）抑制剂L-NAME的影响。我们建议血管周围感觉神经上的CaSR通过涉及CGRP和NK1受体激活的NO产生和KATP通道的内皮依赖性和非依赖性机制介导大鼠肠系膜动脉的舒张。分别。
