Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo

Merlijn J. P. M. T. Meens; Nadine J. A. Mattheij; Jelly Nelissen; Pieter Lemkens; Matthijs G. Compeer; Ben J. A. Janssen; Jo G. R. De Mey

doi:10.1161/HYPERTENSIONAHA.110.169128

Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo

Merlijn J. P. M. T. Meens, Nadine J. A. Mattheij, Jelly Nelissen, Pieter Lemkens, Matthijs G. Compeer, Ben J. A. Janssen, Jo G. R. De Mey^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Slow dissociation of endothelin 1 from its endothelin A receptors is responsible for the long-lasting vasoconstrictor effects of the peptide. We showed recently that calcitonin gene-related peptide selectively terminates long-lasting contractile responses to endothelin 1 in isolated rat mesenteric arteries. Here we assessed whether the antiendothelinergic effect of calcitonin gene-related peptide is vascular bed specific and may terminate long-lasting pressor responses to exogenous and locally produced endothelin 1 in vivo. Regional heterogeneity of the calcitonin gene-related peptide/endothelin A receptor cross-talk was explored in arteries isolated from various rat organs. Endothelin A receptor-mediated arterial contractions were terminated by calcitonin gene-related peptide in rat mesenteric, renal, and spermatic arteries but not in basilar, coronary, epigastric, gastric, splenic, and saphenous arteries. Endothelin A receptor antagonism only ended endothelin 1-induced contractions in spermatic arteries. In anesthetized rats, instrumented with Doppler flow probes to record regional blood flows, long-lasting pressor and vasoconstrictor responses to an intravenous bolus injection of endothelin 1 or big endothelin 1 were transiently reduced by sodium nitroprusside (NO donor) but terminated by intravenously administered calcitonin gene-related peptide. In conscious rats, calcitonin gene-related peptide but not sodium nitroprusside terminated prolonged (>60-minute) pressor responses to endothelin 1 but not those to intravenous infusion of phenylephrine. In conclusion, pressor responses to circulating and locally produced endothelin 1 that are resistant to endothelin receptor antagonism and NO can be terminated by a regionally selective effect of calcitonin gene-related peptide. Calcitonin gene related peptide receptor agonism may represent a novel strategy to treat endothelin 1-associated cardiovascular pathologies. (Hypertension. 2011;58:99-106.) . Online Data Supplement

Original language	English
Pages (from-to)	99-U181
Journal	Hypertension
Volume	58
Issue number	1
DOIs	https://doi.org/10.1161/HYPERTENSIONAHA.110.169128
Publication status	Published - Jul 2011

Keywords

endothelin 1
CGRP
vasculature
ET(A)
vascular resistance

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10.1161/HYPERTENSIONAHA.110.169128

Cite this

@article{2107c6696dbd47a8a3c9ba643fad51ac,

title = "Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo",

abstract = "Slow dissociation of endothelin 1 from its endothelin A receptors is responsible for the long-lasting vasoconstrictor effects of the peptide. We showed recently that calcitonin gene-related peptide selectively terminates long-lasting contractile responses to endothelin 1 in isolated rat mesenteric arteries. Here we assessed whether the antiendothelinergic effect of calcitonin gene-related peptide is vascular bed specific and may terminate long-lasting pressor responses to exogenous and locally produced endothelin 1 in vivo. Regional heterogeneity of the calcitonin gene-related peptide/endothelin A receptor cross-talk was explored in arteries isolated from various rat organs. Endothelin A receptor-mediated arterial contractions were terminated by calcitonin gene-related peptide in rat mesenteric, renal, and spermatic arteries but not in basilar, coronary, epigastric, gastric, splenic, and saphenous arteries. Endothelin A receptor antagonism only ended endothelin 1-induced contractions in spermatic arteries. In anesthetized rats, instrumented with Doppler flow probes to record regional blood flows, long-lasting pressor and vasoconstrictor responses to an intravenous bolus injection of endothelin 1 or big endothelin 1 were transiently reduced by sodium nitroprusside (NO donor) but terminated by intravenously administered calcitonin gene-related peptide. In conscious rats, calcitonin gene-related peptide but not sodium nitroprusside terminated prolonged (>60-minute) pressor responses to endothelin 1 but not those to intravenous infusion of phenylephrine. In conclusion, pressor responses to circulating and locally produced endothelin 1 that are resistant to endothelin receptor antagonism and NO can be terminated by a regionally selective effect of calcitonin gene-related peptide. Calcitonin gene related peptide receptor agonism may represent a novel strategy to treat endothelin 1-associated cardiovascular pathologies. (Hypertension. 2011;58:99-106.) . Online Data Supplement",

keywords = "endothelin 1, CGRP, vasculature, ET(A), vascular resistance",

author = "Meens, {Merlijn J. P. M. T.} and Mattheij, {Nadine J. A.} and Jelly Nelissen and Pieter Lemkens and Compeer, {Matthijs G.} and Janssen, {Ben J. A.} and {De Mey}, {Jo G. R.}",

year = "2011",

month = jul,

doi = "10.1161/HYPERTENSIONAHA.110.169128",

language = "English",

volume = "58",

pages = "99--U181",

journal = "Hypertension",

issn = "0194-911X",

publisher = "LIPPINCOTT WILLIAMS & WILKINS",

number = "1",

}

TY - JOUR

T1 - Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo

AU - Meens, Merlijn J. P. M. T.

AU - Mattheij, Nadine J. A.

AU - Nelissen, Jelly

AU - Lemkens, Pieter

AU - Compeer, Matthijs G.

AU - Janssen, Ben J. A.

AU - De Mey, Jo G. R.

PY - 2011/7

Y1 - 2011/7

N2 - Slow dissociation of endothelin 1 from its endothelin A receptors is responsible for the long-lasting vasoconstrictor effects of the peptide. We showed recently that calcitonin gene-related peptide selectively terminates long-lasting contractile responses to endothelin 1 in isolated rat mesenteric arteries. Here we assessed whether the antiendothelinergic effect of calcitonin gene-related peptide is vascular bed specific and may terminate long-lasting pressor responses to exogenous and locally produced endothelin 1 in vivo. Regional heterogeneity of the calcitonin gene-related peptide/endothelin A receptor cross-talk was explored in arteries isolated from various rat organs. Endothelin A receptor-mediated arterial contractions were terminated by calcitonin gene-related peptide in rat mesenteric, renal, and spermatic arteries but not in basilar, coronary, epigastric, gastric, splenic, and saphenous arteries. Endothelin A receptor antagonism only ended endothelin 1-induced contractions in spermatic arteries. In anesthetized rats, instrumented with Doppler flow probes to record regional blood flows, long-lasting pressor and vasoconstrictor responses to an intravenous bolus injection of endothelin 1 or big endothelin 1 were transiently reduced by sodium nitroprusside (NO donor) but terminated by intravenously administered calcitonin gene-related peptide. In conscious rats, calcitonin gene-related peptide but not sodium nitroprusside terminated prolonged (>60-minute) pressor responses to endothelin 1 but not those to intravenous infusion of phenylephrine. In conclusion, pressor responses to circulating and locally produced endothelin 1 that are resistant to endothelin receptor antagonism and NO can be terminated by a regionally selective effect of calcitonin gene-related peptide. Calcitonin gene related peptide receptor agonism may represent a novel strategy to treat endothelin 1-associated cardiovascular pathologies. (Hypertension. 2011;58:99-106.) . Online Data Supplement

AB - Slow dissociation of endothelin 1 from its endothelin A receptors is responsible for the long-lasting vasoconstrictor effects of the peptide. We showed recently that calcitonin gene-related peptide selectively terminates long-lasting contractile responses to endothelin 1 in isolated rat mesenteric arteries. Here we assessed whether the antiendothelinergic effect of calcitonin gene-related peptide is vascular bed specific and may terminate long-lasting pressor responses to exogenous and locally produced endothelin 1 in vivo. Regional heterogeneity of the calcitonin gene-related peptide/endothelin A receptor cross-talk was explored in arteries isolated from various rat organs. Endothelin A receptor-mediated arterial contractions were terminated by calcitonin gene-related peptide in rat mesenteric, renal, and spermatic arteries but not in basilar, coronary, epigastric, gastric, splenic, and saphenous arteries. Endothelin A receptor antagonism only ended endothelin 1-induced contractions in spermatic arteries. In anesthetized rats, instrumented with Doppler flow probes to record regional blood flows, long-lasting pressor and vasoconstrictor responses to an intravenous bolus injection of endothelin 1 or big endothelin 1 were transiently reduced by sodium nitroprusside (NO donor) but terminated by intravenously administered calcitonin gene-related peptide. In conscious rats, calcitonin gene-related peptide but not sodium nitroprusside terminated prolonged (>60-minute) pressor responses to endothelin 1 but not those to intravenous infusion of phenylephrine. In conclusion, pressor responses to circulating and locally produced endothelin 1 that are resistant to endothelin receptor antagonism and NO can be terminated by a regionally selective effect of calcitonin gene-related peptide. Calcitonin gene related peptide receptor agonism may represent a novel strategy to treat endothelin 1-associated cardiovascular pathologies. (Hypertension. 2011;58:99-106.) . Online Data Supplement

KW - endothelin 1

KW - CGRP

KW - vasculature

KW - ET(A)

KW - vascular resistance

U2 - 10.1161/HYPERTENSIONAHA.110.169128

DO - 10.1161/HYPERTENSIONAHA.110.169128

M3 - Article

C2 - 21606388

SN - 0194-911X

VL - 58

SP - 99-U181

JO - Hypertension

JF - Hypertension

IS - 1

ER -