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Carlton-Carew, Simonette R. E., Greenberg, Harry Z. E., Connor, Eleanor J., Zadeh, Pooneh, Greenwood, Iain A. and Albert, Anthony P. 
ORCID: https://orcid.org/0000-0002-3596-9634
(2024)
Stimulation of the calcium-sensing receptor induces relaxations of rat mesenteric arteries by endothelium-dependent and -independent pathways via BKCa and KATP channels.
Physiological Reports, 12 (2).
ISSN 2051-817X
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Abstract
Stimulation of the calcium-sensing receptor (CaSR) induces both vasoconstrictions and vasorelaxations but underlying cellular processes remain unclear. This study investigates expression and effect of stimulating the CaSR by increasing external Ca2+ concentration ([Ca2+]o) on contractility of rat mesenteric arteries. Immunofluorescence studies showed expression of the CaSR in perivascular nerves, vascular smooth muscle cells (VSMCs), and vascular endothelium cells. Using wire myography, increasing [Ca2+]o from 1 to 10 mM induced vasorelaxations which were inhibited by the calcilytic Calhex-231 and partially dependent on a functional endothelium. [Ca2+]o-induced vasorelaxations were reduced by endothelial NO synthase (eNOS, L-NAME) and large conductance Ca2+-activated K+ channels (BKCa, iberiotoxin), with their inhibitory action requiring a functional endothelium. [Ca2+]o-induced vasorelaxations were also markedly inhibited by an ATP-dependent K+ channel (KATP) blocker (PNU37883), which did not require a functional endothelium to produce its inhibitory action. Inhibitor studies also suggested contributory roles for inward rectifying K+ channels (Kir), Kv7 channels, and small conductance Ca2+-activated K+ channels (SKCa) on [Ca2+]o-induced vasorelaxations. These findings indicate that stimulation of the CaSR mediates vasorelaxations involving multiple pathways, including an endothelium-dependent pathway involving NO production and activation of BKCa channels and an endothelium-independent pathway involving stimulation of KATP channels.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: This work was supported by a British Heart Foundation PhD Studentships for H. Z. E. Greenberg (FS/13/10/30021 to A.P.A) and S.R.E.C‐C (FS/17/40/32942 to A.P.A) and by the Biotechnology and Biological Sciences Research Council (BB/J007226/1 to A.P.A). Publisher Copyright: © 2024 The Authors. Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society. |
| Uncontrolled Keywords: | bk channels,calcium-sensing receptor,endothelial cells,k channels,nitric oxide,perivascular nerves,vascular smooth muscle,physiology,physiology (medical) ,/dk/atira/pure/subjectarea/asjc/1300/1314 |
| Faculty \ School: | Faculty of Medicine and Health Sciences > Norwich Medical School |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 01 Nov 2024 16:30 |
| Last Modified: | 21 Nov 2024 03:32 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/97432 |
| DOI: | 10.14814/phy2.15926 |
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