Two subtypes of the endothelin receptor (ETA and ETB) mediate vasoconstriction in the perfused rat heart.
The effects of endothelin-1 (ET-1) are mediated by two subclasses of the endothelin receptor, ETA and ETB. The Langendorff perfused rat heart was used to determine the endothelin receptor subtype mediating rat coronary vasoconstriction. ET-1 (EC50 = 1.5 x 10(-10) M) and endothelin-3 (ET-3) (10(-11)-3 x 10(-8) M) caused dose-dependent increases in coronary perfusion pressure. BQ-123, a selective antagonist of the ETA-receptor subtype, did not cause a parallel shift in the dose-response curves of ET-1 or ET-3. In the presence of 1-3 x 10(-6) M BQ-123, ET-1 and ET-3 exhibited biphasic dose-response curves, suggesting that vasoconstriction was caused by two receptors. The ETB-selective agonist Suc-[Glu9,Ala11,15]-ET-1(8-21) (IRL 1620) maximally increased perfusion pressure by approximately 50% of the maximal response to ET-1 and was not inhibited by BQ-123. These data suggest that the rat coronary vasoconstrictor effects of ET-1 and ET-3 are mediated by both ETA and ETB receptors.
Balwierczak
J L
JL
Research Department, Ciba-Geigy Corporation, Summit, NJ 07901.
D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D016232:Endothelins / Q000494:pharmacology; D006321:Heart / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology; D010456:Peptides, Cyclic / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017466:Receptors, Endothelin / Q000187:drug effects*; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D016232:Endothelins; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D017466:Receptors, Endothelin; C074308:sovateltide; C072247:cyclo(Trp-Asp-Pro-Val-Leu)