JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, cilt.64, sa.6, ss.567-573, 2014 (SCI-Expanded)
There is evidence that phenolic structure may have biological functions. Ellagic acid (EA), a phenolic compound, has been suggested to have cardioprotective effects. EA effects were investigated on cardiac Ca2+ currents and contractility in rat ventricular myocytes to elucidate the underlying mechanisms. Freshly isolated ventricular myocytes from rat hearts were used. EA dose-dependently reduced Ca2+ currents (I-CaL) with EC50 = 23 nM, whereas it did not affect the inactivation and reactivation parameters. Inhibition of adenylate cyclase by SQ-22536 (10 M) and probucol (5 M) had no effect on EA modulation of I-CaL. Nitric oxide synthase block by L-NAME (500 M) and of guanylate cyclase by ODQ (1 M) abolished EA inhibitory effects on I-CaL. Moreover, EA blunted ventricular myocytes' fractional shortening in a concentration-dependent manner. In conclusion, EA affects ionic and mechanical properties of rat ventricular myocytes starting at nanomolar concentrations. EA suppresses I-CaL and exerts negative inotropic effects through activation of NOS-GC-cGMP pathways. Thus, EA may be useful in pathophysiological conditions such as hypertension and ischemic heart diseases.