Eg. Mcmahon et al., EFFECTS OF SC-52458, AN ANGIOTENSIN AT(1) RECEPTOR ANTAGONIST, IN THEDOG, American journal of hypertension, 10(6), 1997, pp. 671-677
We have previously reported on the basic pharmacologic properties of S
C-52458 yl)methyl]-2-[2-(1H-tetrazol-5-ylphenyl]pyridine), a novel ang
iotensin (All) receptor antagonist that binds potently to AT(1) recept
ors in rat adrenal cortex and blocks AII-mediated contraction in isola
ted rabbit aorta. In the present study, the ability of SC-52458 to blo
ck AII presser responses in conscious dogs was measured. In addition,
we determined whether SC-52458 lowered mean arterial pressure in dogs
with 2 kidney/1 clip renal hypertension when given daily for 4 days, I
n conscious, normotensive dogs, SC-52458 at 30 mg/kg orally, blocked t
he presser response to AII (50 ng/kg, intravenously) with maximal inhi
bition (91%) observed 2 h after dosing, Plasma concentrations of SC-52
458 measured by HPLC also were highest at the 2-h time point. After 24
h, the AII presser response remained inhibited (by 35%) and SC-52458
was still measurable in plasma from treated dogs. In dogs made hyperte
nsive by constriction of the left renal artery, SC-52458 lowered mean
arterial pressure compared to vehicle treatment although heart rate wa
s not different in the two groups. The maximal blood pressure lowering
achieved with SC-52458 was similar to the maximal effect observed wit
h the angiotensin converting enzyme inhibitor lisinopril. We conclude
that SC-52458 blocks AII mediated presser responses in normotensive, c
onscious dogs and SC-52458 is an efficacious antihypertensive agent in
dogs with 2 kidney/1 clip renal hypertension. (C) 1997 American Journ
al of Hypertension, Ltd.