Ellagic Acid Reduces L-type Ca2(+) Current and Contractility Through Modulation of NO-GC-cGMP Pathways in Rat Ventricular Myocytes

OLĞAR Y., ÖZTÜRK ERBOĞA N., USTA C., Puddu P. E., ÖZDEMİR S.

JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, cilt.64, sa.6, ss.567-573, 2014 (SCI-Expanded) identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 64 Sayı: 6
  • Basım Tarihi: 2014
  • Doi Numarası: 10.1097/fjc.0000000000000153
  • Dergi Adı: JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.567-573
  • Anahtar Kelimeler: ellagic acid, Ca2+ currents, fractional shortening, nitric oxide, ventricular myocytes, DEPENDENT PROTEIN-KINASE, CARDIAC MYOCYTES, PHENOLIC ANTIOXIDANT, NITRIC-OXIDE, CA2+ CURRENT, HEART, HYPERTROPHY, POLYPHENOLS, INHIBITION, METABOLISM
  • Ankara Üniversitesi Adresli: Evet

Özet

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.