Vascular Biology Section, Cardiovascular & Genomics Research Institute, St. George's, University of London, London, UK.
Physiol Rep. 2024 Jun;12(12):e16125. doi: 10.14814/phy2.16125.
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 Ca concentration ([Ca]) from 1 to 10 mM induced vasorelaxations, previously shown to involve the CaSR, which were inhibited by pretreatment with capsaicin. [Ca]-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 [Ca]-induced vasorelaxations occurred when CGRP 8-37 and L733,060 were applied together. [Ca]-induced vasorelaxations in the presence of capsaicin were abolished by the ATP-dependent K channel (K) 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 K channels, respectively.
刺激钙敏感受体（CaSR）可调节血管收缩性，但涉及的细胞机制仍不清楚。本研究探讨了血管周围感觉神经在 CaSR 诱导雄性大鼠肠系膜动脉舒张中的作用。在荧光研究中，突触小体（一种突触小泡标记物）与 CaSR 在动脉节段的外膜层中存在共定位。使用电生理描记法，将外部 Ca 浓度（[Ca]）从 1 增加到 10 mM 会引起血管舒张，先前的研究表明这涉及 CaSR，而用辣椒素预处理可抑制其作用。[Ca]诱导的血管舒张部分被降钙素基因相关肽（CGRP）受体阻滞剂 CGRP 8-37 和 BIBN 4096 以及神经激肽 1（NK1）受体阻滞剂 L733,060 所抑制。CGRP 8-37 的抑制作用需要功能性内皮，而 L733,060 的抑制作用则不需要。当 CGRP 8-37 和 L733,060 一起应用时，可完全抑制[Ca]诱导的血管舒张。在存在辣椒素的情况下，[Ca]诱导的血管舒张被 ATP 依赖性 K 通道（K）阻滞剂 PNU 37883 所消除，但不受内皮一氧化氮合酶（eNOS）抑制剂 L-NAME 的影响。我们认为，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 K 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。
