Calcium sensing receptor: A promising therapeutic target in pulmonary hypertension

Zhang, Jiwei; Li, Qinli; Liao, Pu; Xiao, Rui; Zhu, Liping; Hu, Qinghua

doi:10.1016/j.lfs.2024.122472

Cited by 1 publication

(1 citation statement)

References 85 publications

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“…In the vasculature, the CaSR is proposed to be expressed in perivascular sensory nerves, VSMCs, and VECs and there is significant evidence that stimulation of the CaSR induces vasorelaxations (Awumey et al., 2008 , 2013 ; Bukoski et al., 1997 ; Carlton‐Carew et al., 2024 ; Greenberg et al., 2017 , 2019 ; Greenberg, Jahan, et al., 2016 ; Greenberg, Shi, et al., 2016 ; Ishioka & Bukoski, 1999 ; Loot et al., 2013 ; Mupanomunda et al., 1998 , 1999 ; Tang et al., 2016 ; Thakore & Ho, 2011 ; Wang & Bukoski, 1998 , 1999 ; Weston et al., 2005 , 2008 ), vasoconstrictions (Li et al., 2011 ; Schepelmann et al., 2016 ; Wonneberger et al., 2000 ), and biphasic responses (Ohanian et al., 2005 ). Possible involvement of the CaSR in excessive vasocontraction or vasodilatation may indicates it is a therapeutic target for cardiovascular conditions such as systemic and pulmonary hypertension and septic shock (Guo et al., 2018 ; Sood et al., 2022 ; Zhang et al., 2024 ).…”

Section: Introductionmentioning

confidence: 99%

Stimulation of the calcium‐sensing receptor induces relaxations through CGRP and NK1 receptor‐mediated pathways in male rat mesenteric arteries

Carlton‐Carew,

Greenberg,

Greenwood

et al. 2024

Physiological Reports

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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.

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