As a new anti-anginal agent, ranolazinehas been shown to play a cardioprotective role in regulating myocardial ischemic injury. Given that plasma
norepinephrine (NE) and
brain natriuretic peptide (BNP, also termed
B-type natriuretic peptide-45 in rats) are considered neuron-
hormones to indicate
heart failure progression. This study aims to examine effects of
ranolazine on plasma NE and
BNP-45 of rats with chronic ischemic
heart failure (CHF). CHF was induced by
myocardial infarction following
ligation of a left anterior descending artery in adult Sprague-Dawley rats. We hypothesized that
ranolazine attenuates the elevated levels of NE and
BNP-45 observed in CHF rats thereby leading to improvement of the left ventricular function. Results showed that levels of plasma NE and
BNP-45 were increased in CHF rats 6-8 weeks after
ligation of the coronary artery. Our data demonstrate for the first time that
ranolazine significantly attenuated the augmented NE and
BNP-45 induced by CHF (P<0.05 vs. saline control). In addition, a liner relation was observed between NE/BNP-45levels and left ventricular fractional shortening as indication of left ventricular function (r=0.91 and P<0.01 for NE; and r=0.93 and P<0.01 for BNP-45) after administration of
ranolazine. In conclusion, CHF increases the expression of NE and
BNP-45 in peripheral circulation and these changes are related to the left ventricular function.
Ranolazine improves the left ventricular function likely by decreasing heightened NE and
BNP-45 induced by CHF. Therefore, our data indicate the role played by
ranolazine in improving cardiac function in rats with CHF.