title: Hemodynamic effects of direct angiotensin II blockade compared to converting enzyme inhibition in rat model of heart failure.
abstract: The purpose of this investigation was to compare the chronic effects of converting enzyme inhibition with captopril to direct blockade of angiotensin II (AII) 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 AII 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 less than .01) and 15.8 +/- 2.2 mm Hg (P less than .05), respectively, left ventricular end-diastolic volume index from 2.71 +/- 0.10 to 2.03 +/- 0.17 (P less than .05) and 2.18 +/- 0.15 (P less than .05), respectively; venous compliance increased from 2.27 +/- 0.06 to 2.80 +/- 0.18 (P less than .05) and 3.02 +/- 0.21 mL/mm Hg/kg (P less than .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 AII with DuP 753 or with converting enzyme inhibition with captopril produces similar hemodynamic changes in rats with heart failure after myocardial infarction.
authors.affiliation: Department of Internal Medicine, Tucson Veterans Administration Medical Center, AZ 85723.
authors.forename: T E
authors.initials: TE
authors.lastname: Raya
authors.forename: S J
authors.initials: SJ
authors.lastname: Fonken
authors.forename: R W
authors.initials: RW
authors.lastname: Lee
authors.forename: S
authors.initials: S
authors.lastname: Daugherty
authors.forename: S
authors.initials: S
authors.lastname: Goldman
authors.forename: P C
authors.initials: PC
authors.lastname: Wong
authors.forename: P B
authors.initials: PB
authors.lastname: Timmermans
authors.forename: E
authors.initials: E
authors.lastname: Morkin
mesh_terms: D000284:Administration, Oral; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D002303:Cardiac Output, Low / Q000188:drug therapy*; D003187:Compliance; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006321:Heart / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D013777:Tetrazoles / Q000494:pharmacology*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D007093:Imidazoles; D013777:Tetrazoles; D000804:Angiotensin II; D002216:Captopril; D019808:Losartan