Abstract 1594: Chronic Administration of Endogenous Inotropic Peptide, Apelin, Prevents Left Ventricular Remodeling and Improves Survival in Hypertensive Rats with Heart Failure
Background: The endogenous peptide, apelin, has positive inotropic, vasodilatory and diuretic effects through APJ receptor. We have recently reported that cardiac apelin-APJ system was down-regulated in rats with heart failure and might be counter-regulated by cardiac angiotensin II system. Also, in humans, plasma apelin concentrations are reported to decrease in heart failure. Therefore, we tested the hypothesis that chronic apelin administration would prevent the progression of left ventricular (LV) remodeling and improve the survival in rat heart failure model.
Methods and Results: Dahl salt-sensitive hypertensive rats were given high salt diet from 6 weeks of age. They were chronically treated with apelin (15ug/day) (APL group: n=9) or saline (CONT group: n=11) from the LV hypertrophic stage (11 weeks of age) until 21 weeks. There was no difference in blood pressure between the two groups through the course. The survival rate in APL group was improved at 21 weeks of age from 18.2% to 77.8% (log rank test; p<0.05). By echocardiography, LV end-diastolic dimension was smaller (7.00 ± 0.15mm vs. 8.04 ± 0.76mm; p<0.05) and fractional shortening was preserved (46.2 ± 6.7% vs. 31.5 ± 9.3%; p<0.05) in APL group. In postmortem examination, LV hypertrophy was mildly suppressed (LV weight/body weight, 3.56 ± 0.31mg/g vs. 4.17 ± 0.42mg/g; p<0.05) and pulmonary congestion was suppressed (lung weight/body weight, 4.88 ± 0.98mg/g vs. 7.84 ± 2.66mg/g; p<0.05) in APL group. mRNA levels of BNP and endothelin-1 in LV was significantly decreased in APL group. Although APJ is a G protein-coupled receptor having high similarity with angiotensin II type 1 receptor, exogenous apelin administration did not evoke hypertrophic responses nor did it suppress hypertrophy induced by endothelin-1 in neonatal rat cardiac myocytes.
Conclusions: These results indicate chronic apelin administration has beneficial effects by preventing the progression of LV remodeling and dysfunction without inducing additional LV hypertrophy in rats with heart failure. Modulation of apelin-APJ system might have therapeutic potential in human heart failure.