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This study investigated the role of perivascular sensory nerves in CaSR\u2010induced 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<jats:sup>2+<\/jats:sup> concentration ([Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>) from 1 to 10\u2009mM induced vasorelaxations, previously shown to involve the CaSR, which were inhibited by pretreatment with capsaicin. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>\u2010induced vasorelaxations were partially reduced by the calcitonin gene\u2010related peptide (CGRP) receptor blockers, CGRP 8\u201337 and BIBN 4096, and the neurokinin 1 (NK1) receptor blocker L733,060. The inhibitory effect of CGRP 8\u201337 required a functional endothelium whereas the inhibitory action of L733,060 did not. Complete inhibition of [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>\u2010induced vasorelaxations occurred when CGRP 8\u201337 and L733,060 were applied together. [Ca<jats:sup>2+<\/jats:sup>]<jats:sub>o<\/jats:sub>\u2010induced vasorelaxations in the presence of capsaicin were abolished by the ATP\u2010dependent K<jats:sup>+<\/jats:sup> channel (K<jats:sub>ATP<\/jats:sub>) blocker PNU 37883, but unaffected by the endothelium nitric oxide synthase (eNOS) inhibitor L\u2010NAME. We suggest that the CaSR on perivascular sensory nerves mediate relaxations in rat mesenteric arteries via endothelium\u2010dependent and \u2010independent mechanisms involving CGRP and NK1 receptor\u2010activated NO production and K<jats:sub>ATP<\/jats:sub> channels, respectively.<\/jats:p>","DOI":"10.14814\/phy2.16125","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T03:25:26Z","timestamp":1718940326000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Stimulation of the calcium\u2010sensing receptor induces relaxations through <scp>CGRP<\/scp> and <scp>NK1<\/scp> receptor\u2010mediated pathways in male rat mesenteric arteries"],"prefix":"10.14814","volume":"12","author":[{"given":"Simonette R. 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