title: Competitive antagonism of pressor responses to angiotensin II and angiotensin III by the angiotensin II-1 receptor ligand losartan.
abstract: Losartan (DuP 753) and PD123177 are nonpeptide angiotensin (ANG) receptor ligands for subtypes of ANG II receptors ANG II-1 and ANG II-2, respectively. We examined the effects of losartan and PD123177 on dose - mean arterial pressure (MAP) response curves for ANG II and ANG III in eight groups (n = 6 each) of conscious rats. Saline (0.9% NaCl), losartan (1 x 10(-6) and 9 x 10(-6) mol/kg), and PD123177 (2 x 10(-5) mol/kg) were i.v. bolus injected 15 min before the construction of ANG II dose - response curves in groups I, II, III, and IV, respectively. Groups V-VIII were treated similarly to I-IV except that ANG III was given in place of ANG II. Losartan dose dependently shifted the dose-response curves of ANG II and ANG III to the right with similar dissociation constants (-log KI of 6.6 +/- 0.7 and 6.6 +/- 0.1 mol/kg, respectively) and no change in the maxima. PD123177 affected neither maximum MAP nor ED50 values for ANG II or ANG III. Our results show that losartan but not PD123177 is a competitive antagonist of the MAP effects of ANG II and ANG III.
authors.affiliation: Department of Pharmacology & Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Abdelrahman
authors.forename: C C
authors.initials: CC
authors.lastname: Pang
mesh_terms: D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000805:Angiotensin III / Q000037:antagonists & inhibitors*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D000805:Angiotensin III; D019808:Losartan