"arginine paradox" in cardiomyocytes of Sprague Dawley and spontaneously hypertensive rats: α2-adrenoreceptor-mediated regulation of L-type Ca2+ currents by L-arginine

M. N. Nenov, A. V. Berezhnov, E. I. Fedotova, K. S. Grushin, O. Yu Pimenov, A. N. Murashev, V. P. Zinchenko, Yu M. Kokoz

Research output: Contribution to journalArticle

Abstract

The "arginine paradox" in cardiomyocytes isolated from the left ventricle of Spraque Dawlay (SD) and spontaneously hypertensive rats (SHR) was studied. With 1 mM L-arginine in the bath, the addition of 5 mM L-arginine to incubation medium increased NO production and inhibited amplitude of L-type Ca2+ currents in SD cardiomyocytes. A variety of compounds, including the antagonist of α2-adrenoceptors yohimbine and inhibitors of PI3 kinase (wortmanine), NO synthase (7NI), and cGMP-dependent protein kinase (KT5823), dramatically weakened the inhibitory effects of 5 mM L-arginine on Ca2+ currents. The agonist of α2-adrenoceptors guanabenz acetate increased NO production and inhibited Ca2+ currents, while wortmanine, 7NI, and KT5823 antagonized guanabenz. In SHR cardiomyocytes, the "arginine paradox" was not observed: 5 mM L-arginine affected neither NO production nor Ca2+ currents. Consistently, guanabenz acetate did not alter NO production and inhibited Ca2+ currents to a much smaller extent in SHR cardiomyocytes as compared to SD cardiomyocytes. Taken together, the data of the inhibitory analysis suggest that millimolar L-arginine serves as an agonist of α2-adrenoceptors, which are coupled to PI3K-Akt pathway as well as downstream NO-cGMP pathway to control activity of L-type Ca2+ channels, thus providing new insights into the "arginine paradox" in cardiomyocytes.

Original languageEnglish (US)
Pages (from-to)374-382
Number of pages9
JournalBiochemistry (Moscow) Supplement Series A: Membrane and Cell Biology
Volume4
Issue number4
DOIs
StatePublished - Dec 1 2010

Keywords

  • L-type Ca currents
  • NO-cGMP pathway
  • PI3K-Akt pathway
  • arginine paradox
  • cardiomyocytes
  • α-adrenoceptors

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Cell Biology

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