The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressureCitation formats

  • External authors:
  • M Schepelmann
  • P L Yarova
  • I Lopez-Fernandez
  • T S Davies
  • S C Brennan
  • P J Edwards
  • A Aggarwal
  • J Graça
  • K Rietdorf
  • V Matchkov
  • R A Fenton
  • W Chang
  • M Krssak
  • A Stewart
  • K J Broadley
  • S A Price
  • D H Edwards
  • Paul J. Kemp
  • D Riccardi

Standard

The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. / Schepelmann, M; Yarova, P L; Lopez-Fernandez, I; Davies, T S; Brennan, S C; Edwards, P J; Aggarwal, A; Graça, J; Rietdorf, K; Matchkov, V; Fenton, R A; Chang, W; Krssak, M; Stewart, A; Broadley, K J; Ward, Donald; Price, S A; Edwards, D H; Kemp, Paul J.; Riccardi, D.

In: American journal of physiology. Cell physiology, Vol. 310, No. 3, ajpcell.00248.2015, 01.02.2016, p. C193-204.

Research output: Contribution to journalArticle

Harvard

Schepelmann, M, Yarova, PL, Lopez-Fernandez, I, Davies, TS, Brennan, SC, Edwards, PJ, Aggarwal, A, Graça, J, Rietdorf, K, Matchkov, V, Fenton, RA, Chang, W, Krssak, M, Stewart, A, Broadley, KJ, Ward, D, Price, SA, Edwards, DH, Kemp, PJ & Riccardi, D 2016, 'The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure', American journal of physiology. Cell physiology, vol. 310, no. 3, ajpcell.00248.2015, pp. C193-204. https://doi.org/10.1152/ajpcell.00248.2015, https://doi.org/10.1152/ajpcell.00248.2015

APA

Schepelmann, M., Yarova, P. L., Lopez-Fernandez, I., Davies, T. S., Brennan, S. C., Edwards, P. J., ... Riccardi, D. (2016). The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. American journal of physiology. Cell physiology, 310(3), C193-204. [ajpcell.00248.2015]. https://doi.org/10.1152/ajpcell.00248.2015, https://doi.org/10.1152/ajpcell.00248.2015

Vancouver

Schepelmann M, Yarova PL, Lopez-Fernandez I, Davies TS, Brennan SC, Edwards PJ et al. The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. American journal of physiology. Cell physiology. 2016 Feb 1;310(3):C193-204. ajpcell.00248.2015. https://doi.org/10.1152/ajpcell.00248.2015, https://doi.org/10.1152/ajpcell.00248.2015

Author

Schepelmann, M ; Yarova, P L ; Lopez-Fernandez, I ; Davies, T S ; Brennan, S C ; Edwards, P J ; Aggarwal, A ; Graça, J ; Rietdorf, K ; Matchkov, V ; Fenton, R A ; Chang, W ; Krssak, M ; Stewart, A ; Broadley, K J ; Ward, Donald ; Price, S A ; Edwards, D H ; Kemp, Paul J. ; Riccardi, D. / The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure. In: American journal of physiology. Cell physiology. 2016 ; Vol. 310, No. 3. pp. C193-204.

Bibtex

@article{1eb00854e4534c64b6eecdc1bd664f10,
title = "The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure",
abstract = "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(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with 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 aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with 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 nitric oxide-synthase inhibition with nitro-l-arginine methyl ester 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.",
keywords = "Animals, Aorta, Blood Pressure, Bradycardia, Calcium, Calcium Signaling, Dose-Response Relationship, Drug, Genetic Predisposition to Disease, Heart Rate, Hypotension, Mesenteric Arteries, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Muscle, Smooth, Vascular, Myocytes, Cardiac, Phenotype, Receptors, G-Protein-Coupled, Vasoconstriction, Vasoconstrictor Agents, Vasodilation, Vasodilator Agents, Ventricular Remodeling, Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.",
author = "M Schepelmann and Yarova, {P L} and I Lopez-Fernandez and Davies, {T S} and Brennan, {S C} and Edwards, {P J} and A Aggarwal and J Gra{\cc}a and K Rietdorf and V Matchkov and Fenton, {R A} and W Chang and M Krssak and A Stewart and Broadley, {K J} and Donald Ward and Price, {S A} and Edwards, {D H} and Kemp, {Paul J.} and D Riccardi",
year = "2016",
month = "2",
day = "1",
doi = "10.1152/ajpcell.00248.2015",
language = "English",
volume = "310",
pages = "C193--204",
journal = "American Journal of Physiology: Cell Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "3",

}

RIS

TY - JOUR

T1 - The vascular Ca2+-sensing receptor regulates blood vessel tone and blood pressure

AU - Schepelmann, M

AU - Yarova, P L

AU - Lopez-Fernandez, I

AU - Davies, T S

AU - Brennan, S C

AU - Edwards, P J

AU - Aggarwal, A

AU - Graça, J

AU - Rietdorf, K

AU - Matchkov, V

AU - Fenton, R A

AU - Chang, W

AU - Krssak, M

AU - Stewart, A

AU - Broadley, K J

AU - Ward, Donald

AU - Price, S A

AU - Edwards, D H

AU - Kemp, Paul J.

AU - Riccardi, D

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(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with 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 aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with 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 nitric oxide-synthase inhibition with nitro-l-arginine methyl ester 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(Δflox/Δflox) [knockout (KO)] mice showed an endothelium-independent reduction in aorta and mesenteric artery contractility of KO compared with 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 aortas. Accordingly, diastolic and mean arterial blood pressures of KO animals were significantly reduced compared with 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 nitric oxide-synthase inhibition with nitro-l-arginine methyl ester 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.

KW - Animals

KW - Aorta

KW - Blood Pressure

KW - Bradycardia

KW - Calcium

KW - Calcium Signaling

KW - Dose-Response Relationship, Drug

KW - Genetic Predisposition to Disease

KW - Heart Rate

KW - Hypotension

KW - Mesenteric Arteries

KW - Mice, 129 Strain

KW - Mice, Inbred C57BL

KW - Mice, Knockout

KW - Muscle, Smooth, Vascular

KW - Myocytes, Cardiac

KW - Phenotype

KW - Receptors, G-Protein-Coupled

KW - Vasoconstriction

KW - Vasoconstrictor Agents

KW - Vasodilation

KW - Vasodilator Agents

KW - Ventricular Remodeling

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

KW - Research Support, U.S. Gov't, Non-P.H.S.

U2 - 10.1152/ajpcell.00248.2015

DO - 10.1152/ajpcell.00248.2015

M3 - Article

VL - 310

SP - C193-204

JO - American Journal of Physiology: Cell Physiology

JF - American Journal of Physiology: Cell Physiology

SN - 0363-6143

IS - 3

M1 - ajpcell.00248.2015

ER -