Abstract 12026: Beneficial Effect of Combination of Losartan and Hydrochlorothiazide on Diastolic Heart Failure is Independent of Antihypertensive Effect: A Study Using Dahl Salt-Sensitive Rats
Background: Although therapeutic strategy for diastolic heart failure (DHF) has not been established, recent studies have suggested that combination of angiotensin II receptor blocker (ARB) and hydrochlorothiazide (HCTZ) may be more beneficial than ARB alone. However, it is undeniable that the beneficial effect is due to its strong antihypertensive effect. In order to confirm cardioprotective effects of combination therapy independent of blood pressure, we compared cardiac function and myocardial fibrosis between the combination of ARB (losartan) and HCTZ group and calcium channel blocker (CCB) group 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 = 11), those medicated with CCB (amlodipine 10 mg/kg/day, n = 6), 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 fractional shortening and early diastolic mitral annular velocity (e’) were measured. After the end of the protocol, degree of myocardial fibrosis was assessed by histological studies.
Results: At 17 weeks old, the HS group showed signs of DHF with decreased e’ despite preserved fractional shortening. Compared to 8 weeks old, systolic blood pressure (SBP) did not elevate at 17 weeks old similarly in the CCB group and in the ARB + HCTZ group. However, e’ in in the CCB group decreased at 17 weeks old suggesting impaired diastolic function, whereas it did not in the ARB + HCTZ group. The degree of myocardial fibrosis in the ARB + HCTZ group was lower than that in the CCB group (CCB vs. ARB+HCTZ: 7.0±0.6 vs. 5.1±0.5%, p ≤ 0.05).
Conclusion: Combination therapy prevented progression of diastolic heart failure and reduced myocardial fibrosis independent of antihypertensive effect.
- © 2013 by American Heart Association, Inc.