Role of nitric oxide and protein kinase C in ACh-induced cardioprotection

Huiping Liu, Bradley C. McPherson, Xiangdong Zhu, Mark L A Da Costa, Valluvan Jeevanandam, Zhenhai Yao*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

We examined the roles of nitric oxide and protein kinase C (PKC) in ACh-produced protection of cultured cardiomyocytes during simulated ischemia and reoxygenation. Cell viability was quantified using propidium iodide in chick embryonic ventricular myocytes. O2 radicals were quantified using 2′,7′-dichlorofluorescin diacetate. After a 10-min infusion of ACh (0.5 or 1 mM) and a 10-min drug-free period, we simulated ischemia for 1 h and reoxygenation for 3 h. ACh reduced cardiocyte death [32 ± 4%; n = 6 and 23 ± 4%; n = 7 (P < 0.05)] and attenuated oxidant stress during ischemia and reoxygenation in a concentration-dependent manner compared with controls (47 ± 4%; n = 8; P < 0.05). The increase in O2 radicals before simulated ischemia [357 ± 49; n = 4 and 528 ± 52; n = 8 vs. 211 ± 34; n = 8; P < 0.05 (arbitrary units)] was abolished by the specific nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME) and was markedly attenuated by NG-monomethyl-L-arginine (LNMMA). L-NAME or L-NMMA blocked the protective effects of ACh, which selectively increased PKC-ε isoform activity in the particulate fraction. The PKC inhibitor Gö-6976 had no effect on O2 radical production before simulated ischemia but it abolished the protection; therefore nitric oxide is a large component of ACh-generated O2 radicals. Nitric oxide and O2 radicals activate the PKC-ε isoform by which ACh protects against injury.

Original languageEnglish (US)
Pages (from-to)H191-H197
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume281
Issue number1 50-1
DOIs
StatePublished - 2001

Keywords

  • Cardiomyocytes
  • Ischemia
  • Oxygen radicals
  • Reperfusion

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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