Two dissimilar AT(1) agonists distinctively activate AT(1) receptors located on the luminal membrane of coronary endothelium.
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.
Castillo-Hernández
Jesús
J
Fac. de Medicina de la UASLP, Mexico. jesusramon66@yahoo.com
Torres-Tirado
David
D
Barajas-Espinosa
Alma
A
Chi-Ahumada
Erika
E
Ramiro-Díaz
Juan
J
Ceballos
Guillermo
G
Rubio
Rafael
R
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
D044140:Receptor, Angiotensin, Type 1; D000804:Angiotensin II; D012504:Saralasin; D019808:Losartan