Abstract 12779: Effect of Combination of Losartan and Hydrochlorothiazide on Diastolic Heart Failure in Dahl Salt-Sensitive Rats

Abstract

Background: Therapeutic strategy for diastolic heart failure (DHF) has not been established. Because angiotensin II receptor blocker (ARB) has cardioprotective effects and hydrochlorothiazide (HCTZ) enhances antihypertensive effect, it is expected the combination of these drugs is more beneficial for DHF than ARB alone. We investigated effects of ARB (losartan) and the combination of losartan and HCTZ on cardiac function and myocardial fibrosis in DHF model rats.

Methods: Dahl salt-sensitive rats fed 8% NaCl diet from age 5 weeks were used as DHF model. They were randomly assigned to rats without medication (HS, n = 7), those medicated with ARB (losartan 30 mg/kg/day, n = 8), and those with ARB and HCTZ (losartan 30 mg/kg/day + HCTZ 10 mg/kg/day, n = 6). Measurements of blood pressure and echocardiography were performed at 5, 8, and 17 weeks old. Echocardiographic parameters including left ventricular mass/body weight (LV mass/BW) and early diastolic mitral annular velocity (e’) were measured. Systolic global radial and circumferential strain (GRS, GCS) were also measured using speckle tracking echocardiography. After the end of the protocol, degree of myocardial fibrosis was assessed by histological studies.

Results: At 17 weeks old, the HS group rats showed signs of DHF with decreased e’ despite preserved fractional shortening. Compared to 8 weeks old, systolic blood pressure (SBP) increased and e’ decreased significantly at 17 weeks old in the ARB group. In contrast, in the ARB + HCTZ group, SBP did not increase and e’ did not decrease at 17 weeks old. Although LV mass/BW in the ARB group was not changed, it decreased significantly in the ARB + HCTZ group. There were no differences in the change of GRS and GCS in the ARB group and in the ARB + HCTZ group. The degree of myocardial fibrosis in ARB + HCTZ group was lower than that in the ARB group (5.1±0.5 vs. 7.6±0.6%, p < 0.05).

Conclusions: Combination therapy reduced LV mass and myocardial fibrosis and might be effective on DHF.