Hypertension, Vol 18, 278-288, Copyright © 1991 by American Heart Association
B Bunkenburg, C Schnell, HP Baum, F Cumin and JM Wood
The present study examines the effects of prolonged angiotensin II
antagonism in spontaneously hypertensive rats by using an angiotensin II
receptor antagonist (DuP 753) that is devoid of agonistic properties and
selective for the subtype 1 of the angiotensin II (AT1) receptor. The
antihypertensive effects of DuP 753 and its effects on circulating
parameters of the renin-angiotensin system were compared with those of a
converting enzyme inhibitor (benazeprilat). To minimize any influence of
differences in the pharmacokinetic properties of the two blockers,
administration was by continuous intravenous infusion. The experiments were
performed in conscious, freely moving rats with continuous 24-hour
monitoring of blood pressure. DuP 753 (10 or 30 mg/kg/day) lowered mean
arterial pressure to the same extent as benazeprilat (3 or 10 mg/kg/day)
during a 48-hour period. The antihypertensive effect was sustained when the
treatment was extended to 7 days (DuP 753, 10 mg/kg/day; benazeprilat, 3
mg/kg/day). Neither of the compounds affected the baseline or diurnal
rhythm of heart rate. Plasma concentrations of renin and angiotensin II
were increased sevenfold and 10-fold, respectively, in the rats treated
with DuP 753. In rats treated with benazeprilat, plasma renin concentration
increased threefold, whereas angiotensin II was unchanged. Heart weights
were significantly reduced to a similar extent by DuP 753 and benazeprilat.
Both compounds also induced a smaller but significant decrease in blood
pressure in Wistar-Kyoto rats. Our results indicate that the
antihypertensive effects of converting enzyme inhibitors in spontaneously
hypertensive rats are mainly due to the blockade of the renin-angiotensin
system. In this rat model, angiotensin II appears to play an important role
in the maintenance of hypertension that is mediated via the AT1 receptor.
ARTICLES
Prolonged angiotensin II antagonism in spontaneously hypertensive rats. Hemodynamic and biochemical consequences
Department of Cardiovascular Research, CIBA-GEIGY Limited, Basel, Switzerland.
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