Cardiovascular effects of L-158,809, a new angiotensin type 1 receptor antagonist, assessed using the halothane-anesthetized in vivo canine model.
L-158,809 is a new angiotensin II type 1 receptor antagonist. We simultaneously assessed its antagonistic potency and cardiovascular effects with the halothane-anesthetized in vivo canine model (n = 5). L-158,809 was intravenously infused over 10 min at escalating doses of 0.03, 0.3 and 3 mg/kg. Angiotensin II (0.1 microg/kg, i.v.)-induced vasopressor and negative inotropic responses were significantly suppressed from the low dose L-158,809. Meanwhile, L-158,809 did not affect any of the cardiovascular parameters except that QTc was slightly shortened after the high dose administration. These results support the previous in vitro knowledge that L-158,809 is a highly selective angiotensin II receptor antagonist.
Yoneyama
Masahiko
M
Department of Pharmacology, Yamanashi Medical University, Japan.
Sugiyama
Atsushi
A
Yoshida
Hiroshi
H
Satoh
Yoshioki
Y
Hashimoto
Keitaro
K
D000804:Angiotensin II / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006221:Halothane / Q000008:administration & dosage*; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D023421:Models, Animal; D011945:Receptors, Angiotensin / Q000378:metabolism; D013777:Tetrazoles / Q000008:administration & dosage / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C070967:L 158809; D006221:Halothane