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

Research output: Contribution to journalJournal articleResearchpeer-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.

Original languageEnglish
JournalHypertension
Volume58
Issue number1
Pages (from-to)99-106
ISSN0194-911X
DOIs
Publication statusPublished - Jul 2011
Externally publishedYes

Keywords

  • Animals
  • Arteries
  • Blood Pressure
  • Calcitonin Gene-Related Peptide
  • Disease Models, Animal
  • Endothelin-1
  • Hypertension
  • Male
  • Rats
  • Rats, Inbred WKY
  • Regional Blood Flow
  • Vasoconstriction
  • Vasodilator Agents

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