Two dissimilar AT1 agonists distinctively activate AT1 receptors located on the luminal membrane of coronary endothelium

Jesús Castillo-Hernández, David Torres-Tirado, Alma Barajas-Espinosa, Erika Chi-Ahumada, Juan Ramiro-Díaz, Guillermo Ceballos, Rafael Rubio

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Diverse intracoronary agonists cause cardiac effects while acting on coronary endothelial luminal membrane (CELM) receptor. Our data show: a) the presence of AT1R in isolated CELM and in all cardiac cell types and b) sustained intracoronary infusions of Ang II-POL, a large sized molecule (~ 15,000 kDa) confined to the vessel lumen that can only act on CELM's AT1R or Ang II (~ 1 kDa); both exert the same maximum positive inotropic (PIE) and coronary constriction (CPP). The effects of these two agonists are blocked by Losartan and by Sar-POL; a large size antagonist (~ 15,000 kDa) that acts only on CELM. Ang II effects are transient due to desensitization and cause tachyphylaxis to Ang II and toward Ang II-POL suggesting that both Ang II and Ang II-POL act on the same receptor group. In contrast, Ang II-POL effects are sustained and do not cause tachyphylaxis. The results show that intravascular Ang II and Ang II-POL act differentially by an unknown mechanism on CELM's AT1R and suggest that intravascular Ang II and Ang II-POL cause PIE and CCP by activation limited to CELM's AT1R through an unknown mechanism that is space-confined to the CELM's AT1R.

Original languageEnglish (US)
Pages (from-to)314-322
Number of pages9
JournalVascular Pharmacology
Issue number5-6
StatePublished - Nov 2009
Externally publishedYes


  • ATR activation without desensitization
  • Compartmentalization of hormone action
  • Desensitization
  • Endothelial luminal AT receptors
  • Tachyphylaxis

ASJC Scopus subject areas

  • Physiology
  • Molecular Medicine
  • Pharmacology


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