A non-competitive type of angiotensin-receptor antagonism by losartan in renal artery preparations.
In rabbit isolated renal artery preparations angiotensin II (1-100 nM) induced concentration-dependent vasoconstriction. Losartan at lower concentrations (3-100 nM) concentration dependently depressed the maximal responses to angiotensin II. At higher concentrations (0.3 and 1 microM) lasartan only shifted the concentration-response curves for angiotensin II to the right without further reducing the maximal responses. PD123177 (1 microM) did not influence angiotensin II-induced contractions. In rabbit renal artery, AT1 but not AT2 receptors appear to mediate the responses to angiotensin II. However, losartan antagonized the AT1 receptors in both an insurmountable and a surmountable manner, possibly involving two subpopulations of AT1 receptors.
Zhang
J
J
Department of Pharmacotherapy, University of Amsterdam, Netherlands.
Pfaffendorf
M
M
Zhang
J S
JS
Van Zwieten
P A
PA
D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D019808:Losartan; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D012077:Renal Artery / Q000187:drug effects* / Q000502:physiology; D013777:Tetrazoles / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects*
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan