Background: Ranolazine is generally used to treat anginal symptoms for
patients with symptomatic chronic stable angina pectoris. By improving ischemiareperfusion,
ranolazine is also observed to have protective effects on myocardial
ischemic injury in animal models. It is noteworthy to find interventions that can decrease
adverse effects of this drug and thereby increase its clinical application.
Methods: In this report, we used a rat model of chronic ischemic heart failure (CHF) to
examine if vagal stimulation can strengthen the effects of ranolazine on worsened
cardiac function in CHF. Plasma norepinephrine (NE) and brain natriuretic peptide [BNP,
termed B-type natriuretic peptide-45 (BNP-45) in rats] are regulated by sympathetic
nerve activity. Because NE and BNP are considered as neurohormones indicating heart
failure progression, we also determined the levels of plasma NE and BNP-45 besides
cardiac function. Moreover, we examined the role of sympathetic pro-inflammatory
cytokines in engagement of vagal activation.
Results: Our data show that ranolazine intraperitoneally improved the impaired left
ventricular function, and attenuated the exaggerated NE/BNP-45 and cytokines (such as
IL-1β, IL-6 and TNF-α) after development of CHF. Particularly, our results show that
vagal activation largely amplified the effects of ranolazine on cardiac function in CHF.
Conclusion: Our data indicate that: 1) ranolazine alleviates sympathetic nerve activity
thereby leading to improvement of the worsened cardiac function in CHF; and 2) vagal
stimulation augments the effect of ranolazine. Accordingly, results of this study have
implications for the role played by a combination of vagal stimulation and ranolazine in
improving cardiac function in CHF.