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*
Pharmacology and Personalised Medicine
CARIM School for Cardiovascular Diseases
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
99-U181
https://doi.org/10.1161/HYPERTENSIONAHA.110.169128
endothelin 1
ET(A)
vascular resistance
10.1161/HYPERTENSIONAHA.110.169128
Meens, M. J. P. M. T., Mattheij, N. J. A., Nelissen, J., Lemkens, P., Compeer, M. G., Janssen, B. J. A., & De Mey, J. G. R. (2011). Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo. Hypertension, 58(1), 99-U181. https://doi.org/10.1161/HYPERTENSIONAHA.110.169128
Meens, Merlijn J. P. M. T. ; Mattheij, Nadine J. A. ; Nelissen, Jelly et al. / Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo. In: Hypertension. 2011 ; Vol. 58, No. 1. pp. 99-U181.
@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.}",
doi = "10.1161/HYPERTENSIONAHA.110.169128",
pages = "99--U181",
journal = "Hypertension",
Meens, MJPMT, Mattheij, NJA, Nelissen, J, Lemkens, P, Compeer, MG, Janssen, BJA & De Mey, JGR 2011, 'Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo', Hypertension, vol. 58, no. 1, pp. 99-U181. https://doi.org/10.1161/HYPERTENSIONAHA.110.169128
Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo. / Meens, Merlijn J. P. M. T.; Mattheij, Nadine J. A.; Nelissen, Jelly et al.
In: Hypertension, Vol. 58, No. 1, 07.2011, p. 99-U181.
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.
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
SP - 99-U181
JO - Hypertension
JF - Hypertension
Meens MJPMT, Mattheij NJA, Nelissen J, Lemkens P, Compeer MG, Janssen BJA et al. Calcitonin Gene-Related Peptide Terminates Long-Lasting Vasopressor Responses to Endothelin 1 In Vivo. Hypertension. 2011 Jul;58(1):99-U181. doi: 10.1161/HYPERTENSIONAHA.110.169128