TY - JOUR
T1 - Hemodynamic effects of direct angiotensin ii blockade compared to converting enzyme inhibition in rat model of heart failure
AU - Raya, Thomas E.
AU - Fonken, Steven J.
AU - Lee, Richard W.
AU - Daugherty, Sherry
AU - Goldman, Steven
AU - Wong, Pancras C.
AU - Timmermans, Pieter B.M.W.M.
AU - Morkin, Eugene
PY - 1991/4
Y1 - 1991/4
N2 - The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (All) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to All parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 ± 1.5 to 14.2 ± 3.0 (P <.01) and 15.8 ± 2.2 mm Hg(P <.05), respectively, left ventricular end-diastolic volume index from 2.71 ± 0.10 to 2.03 ± 0.17 (P <.05) and 2.18 ± 0.15 (P <.05), espectively; venous compliance increased from 2.27 ± 0.06 to 2.80 ± 0.18 (P <.05) and 3.02 ± 0.21 mL/mm Hg/kg (P <.01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 ±1.1 to 59.4 ± 3.0 and 64.9 ± 3.9 mL/kg, respectively. Thus, direct blockade of All with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. Am J Hypertens 1991;4:334S - 340S.
AB - The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (All) with DuP 753 in the rat model of heart failure. Rats with chronic heart failure postinfarction were treated for 2 weeks with either captopril (2 g/L, N = 9) in their drinking water or with DuP 753 (40 mg/kg/day for two weeks by gastric gavage, N = 10), or placebo (N = 9). At this dose, DuP 753 shifted the log dose-pressor response curve to All parallel to the right by two orders of magnitude in both chronically treated normal and heart failure rats. In rats with heart failure, DuP 753 and captopril reduced left ventricular end-diastolic pressure from 26.7 ± 1.5 to 14.2 ± 3.0 (P <.01) and 15.8 ± 2.2 mm Hg(P <.05), respectively, left ventricular end-diastolic volume index from 2.71 ± 0.10 to 2.03 ± 0.17 (P <.05) and 2.18 ± 0.15 (P <.05), espectively; venous compliance increased from 2.27 ± 0.06 to 2.80 ± 0.18 (P <.05) and 3.02 ± 0.21 mL/mm Hg/kg (P <.01), respectively. There were no significant changes in left ventricular weight/body weight ratio, mean aortic pressure, heart rate, or right atrial pressure. There was a trend, but not significant, for a reduction in total blood volume from 65.8 ±1.1 to 59.4 ± 3.0 and 64.9 ± 3.9 mL/kg, respectively. Thus, direct blockade of All with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction. Am J Hypertens 1991;4:334S - 340S.
KW - Afterload reduction
KW - Angiotensin II antagonism
KW - Captopril
KW - DuP 753
KW - Peripheral circulation
KW - Rat heart failure
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U2 - 10.1093/ajh/4.4.334S
DO - 10.1093/ajh/4.4.334S
M3 - Article
C2 - 1854461
AN - SCOPUS:0025856142
VL - 4
SP - 334
EP - 340
JO - American Journal of Hypertension
JF - American Journal of Hypertension
SN - 0895-7061
IS - 4
ER -