title: Two dissimilar AT(1) agonists distinctively activate AT(1) receptors located on the luminal membrane of coronary endothelium.
abstract: Diverse intracoronary agonists cause cardiac effects while acting on coronary endothelial luminal membrane (CELM) receptor. Our data show: a) the presence of AT(1)R in isolated CELM and in all cardiac cell types and b) sustained intracoronary infusions of Ang II-POL, a large sized molecule (approximately 15,000 kDa) confined to the vessel lumen that can only act on CELM's AT(1)R or Ang II (approximately 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 (approximately 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 AT(1)R and suggest that intravascular Ang II and Ang II-POL cause PIE and CCP by activation limited to CELM's AT(1)R through an unknown mechanism that is space-confined to the CELM's AT(1)R.
authors: Fac. de Medicina de la UASLP, Mexico. jesusramon66@yahoo.com
authors: Jesús
authors: J
authors: Castillo-Hernández
authors: David
authors: D
authors: Torres-Tirado
authors: Alma
authors: A
authors: Barajas-Espinosa
authors: Erika
authors: E
authors: Chi-Ahumada
authors: Juan
authors: J
authors: Ramiro-Díaz
authors: Guillermo
authors: G
authors: Ceballos
authors: Rafael
authors: R
authors: Rubio
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1 / Q000819:agonists* / Q000032:analysis / Q000187:drug effects; D012504:Saralasin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
chemical_list: D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D012504:Saralasin; D019808:Losartan