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.
- ATR activation without desensitization
- Compartmentalization of hormone action
- Endothelial luminal AT receptors
ASJC Scopus subject areas
- Molecular Medicine