title: BQ123, an ETA receptor antagonist, attenuates endothelin-1-induced vasoconstriction in rat pulmonary circulation.
abstract: Endothelin-1 (ET-1) is a potent endogenous vasoactive peptide whose role in regulation of vascular tone is unclear. BQ123 is a recently described ETA receptor antagonist which may be useful in further investigation of the physiologic and pathophysiologic significance of ET-1. To test its efficacy in the pulmonary circulation, the vascular response to exogenous ET-1 with and without BQ123 was assessed in rat pulmonary artery (PA) rings and salt-perfused lungs. In both main and distal (250-350 microns ID) PA rings, BQ123 significantly attenuated ET-1-induced contractility, but was more effective in the larger vessels. Likewise, BQ123 significantly blunted ET-1-induced vasoconstriction in perfused lungs by > 80%. In addition, it had no effect on ET-3-mediated or U46619-mediated vasoconstriction, nor did it influence ET-1-induced vasodilation. Development of ET-1-associated hydrostatic edema was also unaffected by BQ123. We conclude that BQ123 effectively attenuates ET-1-induced vasoconstriction in both PA rings and in isolated perfused lungs. The absence of effect of BQ123 on ET-3 vasoconstriction, ET-1 vasodilation, or ET-1- and ET-3-induced hydrostatic edema formation suggests that these processes may be transduced through a non-ETA receptor.
authors.affiliation: Division of Pulmonary Sciences, University of Colorado Health Sciences Center, Denver 80262.
authors.forename: S T
authors.initials: ST
authors.lastname: Bonvallet
authors.forename: M
authors.initials: M
authors.lastname: Oka
authors.forename: M
authors.initials: M
authors.lastname: Yano
authors.forename: M R
authors.initials: MR
authors.lastname: Zamora
authors.forename: I F
authors.initials: IF
authors.lastname: McMurtry
authors.forename: T J
authors.initials: TJ
authors.lastname: Stelzner
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008297:Male; D008969:Molecular Sequence Data; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010477:Perfusion; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044022:Receptor, Endothelin A; D014661:Vasoconstriction / Q000187:drug effects*
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010456:Peptides, Cyclic; D044022:Receptor, Endothelin A; C072247:cyclo(Trp-Asp-Pro-Val-Leu)