title: Functional comparison of the antagonistic properties of some Angiotensin II type 1 receptor blockers on the contraction elicited by Angiotensin II and thromboxane A2 on human saphenous veins.
abstract: We previously described on human vascular preparations that, in addition to its antagonistic properties on Angiotensin II type 1 (AT1) receptor, losartan could also inhibit the contraction elicited by the stable thromboxane A2 mimetic U46619. The present study was designed (1) to investigate, in human vascular preparations (the saphenous veins) whether these antagonistic properties on thromboxane A2/prostaglandin H2 (TP) receptor were shared by some other AT1 receptor antagonists (irbesartan and valsartan) and the active metabolite of losartan EXP3174, and (2) to compare their antagonistic properties on TP receptors to their antagonistic properties on AT1 receptors. In the presence of indomethacin (10 microM) and Nomega-nitro-L-arginine (100 microM), irbesartan, valsartan, and EXP3174 induced a rightward shift of U46619- and angiotensin II-induced contraction. The inhibitory effect of irbesartan, valsartan, and EXP3174 on U46619-induced contraction was significant from 100 microM while their inhibitory effect on the contraction elicited by angiotensin II was significant from 1 nM. With regard to the plasma therapeutic concentrations of irbesartan, valsartan, and EXP3174, these data suggest that TP receptor blockade does not account for the antihypertensive effects of these AT1 receptor blockers.
authors.affiliation: Laboratory of Pharmaclogy, University of Medicine, La Tronche, France.
authors.forename: Ahmed
authors.initials: A
authors.lastname: Hakim
authors.forename: Françoise
authors.initials: F
authors.lastname: Stanke-Labesque
authors.forename: Pascale
authors.initials: P
authors.lastname: Hoffmann
authors.forename: Carmine
authors.initials: C
authors.lastname: Sessa
authors.forename: Françoise
authors.initials: F
authors.lastname: Caron
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Cracowski
authors.forename: Germain
authors.initials: G
authors.lastname: Bessard
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds / Q000494:pharmacology; D004336:Drug Antagonism; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D000077405:Irbesartan; D019808:Losartan; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism; D044244:Receptors, Thromboxane A2, Prostaglandin H2 / Q000037:antagonists & inhibitors*; D012501:Saphenous Vein / Q000187:drug effects / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology; D014633:Valine / Q000031:analogs & derivatives* / Q000494:pharmacology; D000068756:Valsartan
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D001713:Biphenyl Compounds; D007093:Imidazoles; D044244:Receptors, Thromboxane A2, Prostaglandin H2; D013777:Tetrazoles; D000804:Angiotensin II; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000068756:Valsartan; C066026:losartan carboxylic acid; D014633:Valine; D000077405:Irbesartan; D019808:Losartan