title: Effect of losartan on right ventricular hypertrophy and cardiac angiotensin I-converting enzyme activity in pulmonary hypertensive rats.
abstract: The aim of this study was to investigate the effect of prophylactic treatment with the angiotensin type 1 (AT1) receptor antagonist losartan on right ventricular hypertrophy and cardiac angiotensin 1-converting enzyme (ACE) activity in a rat model of monocrotaline-induced pulmonary hypertension. Losartan failed to prevent either pulmonary hypertension or right ventricular hypertrophy. Right ventricular ACE in untreated pulmonary hypertensive rats did not differ from control rats. Losartan treatment in pulmonary hypertensive rats caused a significant 2-fold increase of ACE activity in the hypertrophied right (p < 0.005) but not in the left ventricle. Thus, cardiac ACE activity is not stimulated in rats with monocrotaline-induced right ventricular hypertrophy. Prophylactic losartan treatment in this model of progressive pulmonary hypertension failed to prevent or reduce the increase in ventricular afterload. The relevance of the increase in right ventricular ACE activity during pulmonary hypertension after losartan treatment is unknown and needs to be evaluated in further studies.
authors.affiliation: Max Delbrück Centre (MDC) for Molecular Medicine, Berlin, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Kreutz
authors.forename: M S
authors.initials: MS
authors.lastname: Fernandez-Alfonso
authors.forename: D
authors.initials: D
authors.lastname: Ganten
authors.forename: M
authors.initials: M
authors.lastname: Paul
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001713:Biphenyl Compounds / Q000494:pharmacology*; D006352:Heart Ventricles / Q000201:enzymology*; D006439:Hemodynamics; D006801:Humans; D006976:Hypertension, Pulmonary / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D017380:Hypertrophy, Right Ventricular / Q000188:drug therapy / Q000201:enzymology* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology*; D019808:Losartan; D008297:Male; D007703:Peptidyl-Dipeptidase A / Q000187:drug effects / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000378:metabolism; D012083:Renin / Q000378:metabolism; D013777:Tetrazoles / Q000494:pharmacology*
chemical_list: D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D007703:Peptidyl-Dipeptidase A; D012083:Renin; D019808:Losartan