Reduction of development of left ventricular hypertrophy in salt-loaded Dahl salt-sensitive rats by angiotensin II receptor inhibition

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.