Functional ETA-ETB receptor cross-Talk in basilar artery in Situ from ETB receptor deficient rats

Seonghun Yoon, Cheryl E. Gariepy, Masashi Yanagisawa, Mario Zuccarello, Robert M. Rapoport

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

The role of endothelin (ET) A-ETB receptor cross-Talk in limiting the ETA receptor antagonist inhibition of ET-1 constriction is revealed by the partial or complete dependency of the ETA receptor antagonist inhibition on functional removal of the ETB receptor. Although functional removal of the ETB receptor is generally accomplished with ETB receptor antagonist, a novel approach using rats containing a naturally occurring deletion mutation in the ETB receptor [rescued "spotting lethal" (sl) rats; ETB sl/sl] demonstrated increased ETA receptor antagonist inhibition of ET-1 constriction in vena cava. We investigated whether this deletion mutation was also sufficient to remove the ETB receptor dependency of the ETA receptor antagonist inhibition of ET-1 constriction in the basilar artery. Consistent with previous reports, ET-1 plasma levels were elevated in ETB sl/sl as compared with ETB +/+ rats. ETB receptor antagonist failed to relax the ET-1 constricted basilar artery from ETB +/+ and ETB sl/sl rats. Relaxation to combined ETA and ETB receptor antagonist was greater than relaxation to ETA receptor antagonist in the basilar artery from ETB +/+ and, unexpectedly, ETB sl/sl rats. These findings confirm the presence of ETA-ETB receptor cross-Talk in the basilar artery. We speculate that mutant ETB receptor expression produced by alternative splicing may be sufficient to allow cross-talk.

Original languageEnglish (US)
Pages (from-to)212-217
Number of pages6
JournalJournal of Cardiovascular Pharmacology
Volume67
Issue number3
DOIs
StatePublished - Mar 1 2016

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Keywords

  • basilar artery
  • constriction
  • cross-Talk
  • endothelin receptor
  • endothelin receptor antagonist
  • in situ
  • spotting lethal rat

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

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