Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. / Schepelmann, Martin; Yarova, Polina L; Lopez-Fernandez, Irene et al.
In: American Journal of Physiology: Cell Physiology, Vol. 310, No. 3, 01.02.2016, p. C193-C204.Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaper › Journal article › Research › peer-review
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TY - JOUR
T1 - The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure
AU - Schepelmann, Martin
AU - Yarova, Polina L
AU - Lopez-Fernandez, Irene
AU - Davies, Thomas S
AU - Brennan, Sarah C
AU - Edwards, Peter J
AU - Aggarwal, Abhishek
AU - Graca, Joao
AU - Rietdorf, Katja
AU - Matchkov, Vladimir V
AU - Fenton, Robert A
AU - Chang, Wenhan
AU - Krssak, Martin
AU - Stewart, Andrew
AU - Broadley, Kenneth J
AU - Ward, Donald T
AU - Price, Sally A
AU - Edwards, D H
AU - Kemp, Paul J
AU - Riccardi, Daniela
N1 - Copyright © 2015, American Journal of Physiology - Cell Physiology.
PY - 2016/2/1
Y1 - 2016/2/1
N2 - The extracellular calcium-sensing receptor, CaSR, is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative (wild-type, WT) and Cre-positive (SM22α)CaSR(∆flox/∆flox) (knock-out, KO) mice showed and endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared to WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT, but only relaxation in KO aortae. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared to WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either NO-synthase inhibition with L-NAME or by a high salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.
AB - The extracellular calcium-sensing receptor, CaSR, is expressed in blood vessels where its role is not completely understood. In this study, we tested the hypothesis that the CaSR expressed in vascular smooth muscle cells (VSMC) is directly involved in regulation of blood pressure and blood vessel tone. Mice with targeted CaSR gene ablation from vascular smooth muscle cells (VSMC) were generated by breeding exon 7 LoxP-CaSR mice with animals in which Cre recombinase is driven by a SM22α promoter (SM22α-Cre). Wire myography performed on Cre-negative (wild-type, WT) and Cre-positive (SM22α)CaSR(∆flox/∆flox) (knock-out, KO) mice showed and endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared to WT mice in response to KCl and to phenylephrine. Increasing extracellular calcium ion (Ca(2+)) concentrations (1-5 mM) evoked contraction in WT, but only relaxation in KO aortae. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared to WT, as measured by both tail cuff and radiotelemetry. This hypotension was mostly pronounced during the animals' active phase and was not rescued by either NO-synthase inhibition with L-NAME or by a high salt-supplemented diet. KO animals also exhibited cardiac remodeling, bradycardia and reduced spontaneous activity in isolated hearts and cardiomyocyte-like cells. Our findings demonstrate a role for CaSR in the cardiovascular system and suggest that physiologically relevant changes in extracellular Ca(2+) concentrations could contribute to setting blood vessel tone levels and heart rate by directly acting on the cardiovascular CaSR.
U2 - 10.1152/ajpcell.00248.2015
DO - 10.1152/ajpcell.00248.2015
M3 - Journal article
C2 - 26538090
VL - 310
SP - C193-C204
JO - American Journal of Physiology: Cell Physiology
JF - American Journal of Physiology: Cell Physiology
SN - 0363-6143
IS - 3
ER -