title: Reduction of development of left ventricular hypertrophy in salt-loaded Dahl salt-sensitive rats by angiotensin II receptor inhibition.
abstract: To determine the effect of the angiotensin II AT1 receptor antagonist losartan (DuP753) on echocardiographic left ventricular (LV) anatomy in Dahl rats on high sodium diet, 27 Dahl salt-sensitive (Dahl-S, 13 on drug and 14 receiving tap water) and 27 Dahl salt-resistant rats (Dahl-R, 13 on drug and 14 receiving tap water) were studied by M-mode echocardiography during 8 weeks of 8% NaCl diet. At the endpoint (after 8 weeks or the last echocardiogram for animals who died earlier), Dahl-S receiving losartan had lower LV mass (1.6 +/- 0.4 g/kg 0.59) than Dahl-S receiving tap water (2.2 +/- 0.7 g/kg 0.59; P < .005), although blood pressure was only partially reduced (167 +/- 29 v 195 +/- 52; P = .05). This difference was mainly due to lower LV wall thickness (P < .02), with a less consistent decrease in LV chamber size in Dahl-S receiving losartan. Blood pressure was normal in Dahl-R (tap water group = 116 +/- 11 mm Hg; losartan group = 115 +/- 13 mm Hg) and losartan had no effect on LV mass (1.6 +/- 0.4 g/kg 0.59) in both groups). In the majority of rats, echocardiographic measurements were compared between the end of second or third week and the last available study: LV mass increased in salt-loaded Dahl-S receiving tap water (1.6+/- 0.6 to 2.1 +/- 0.7 g/kg 0.59, P < .04) and was stable in Dahl-S receiving losartan (1.5 +/- 0.1 to 1.5 +/- 0.3 g/kg 0.59), paralleling changes in LV chamber dimension. Thus, a high salt diet leads to hypertension and eccentric LV hypertrophy in Dahl-S but not in Dahl-R. Inhibition of angiotensin II AT1 receptors reduces the development of LV hypertrophy in Dahl-S rats despite lack of efficient control of blood pressure.
authors.affiliation: Department of Medicine, New York Hospital-Cornell Medical Center, New York 10021, USA.
authors.forename: G
authors.initials: G
authors.lastname: de Simone
authors.forename: R B
authors.initials: RB
authors.lastname: Devereux
authors.forename: M J
authors.initials: MJ
authors.lastname: Camargo
authors.forename: D C
authors.initials: DC
authors.lastname: Wallerson
authors.forename: J E
authors.initials: JE
authors.lastname: Sealey
authors.forename: J H
authors.initials: JH
authors.lastname: Laragh
mesh_terms: D000704:Analysis of Variance; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D004452:Echocardiography; D006973:Hypertension / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000000981:diagnostic imaging / Q000209:etiology / Q000517:prevention & control*; D007093:Imidazoles / Q000627:therapeutic use*; D019808:Losartan; D008297:Male; D051381:Rats; D011922:Rats, Mutant Strains; D012189:Retrospective Studies; D017673:Sodium Chloride, Dietary / Q000009:adverse effects*; D013777:Tetrazoles / Q000627:therapeutic use*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D017673:Sodium Chloride, Dietary; D013777:Tetrazoles; D019808:Losartan