"Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats: α2-adrenoreceptormediated 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

3 Citations (Scopus)

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 cGM P-dependent protein kinase (KT5823), dramatically weakened the inhibitory effects of 5 mM ¿-arginine on Ca2+ currents. The agonist of a2-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 ¿-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)440-448
Number of pages9
JournalBiologicheskie Membrany
Volume27
Issue number5
StatePublished - 2010
Externally publishedYes

Fingerprint

Inbred SHR Rats
Cardiac Myocytes
Arginine
Guanabenz
Adrenergic Receptors
Phosphatidylinositol 3-Kinases
Yohimbine
Baths
Nitric Oxide Synthase
Heart Ventricles

Keywords

  • α
  • adrenoceptors
  • Arginine paradox
  • Cardiomyocytes
  • L-type ca currents
  • NO-cGMPpathway
  • PI3K-Akt pathway

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Nenov, M. N., Berezhnov, A. V., Fedotova, E. I., Grushin, K. S., Yu Pimenov, O., Murashev, A. N., ... Kokoz, Y. M. (2010). "Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats: α2-adrenoreceptormediated regulation of L-type Ca2+ currents by L-arginine. Biologicheskie Membrany, 27(5), 440-448.

"Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats : α2-adrenoreceptormediated regulation of L-type Ca2+ currents by L-arginine. / Nenov, M. N.; Berezhnov, A. V.; Fedotova, E. I.; Grushin, K. S.; Yu Pimenov, O.; Murashev, A. N.; Zinchenko, V. P.; Kokoz, Yu M.

In: Biologicheskie Membrany, Vol. 27, No. 5, 2010, p. 440-448.

Research output: Contribution to journalArticle

Nenov, MN, Berezhnov, AV, Fedotova, EI, Grushin, KS, Yu Pimenov, O, Murashev, AN, Zinchenko, VP & Kokoz, YM 2010, '"Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats: α2-adrenoreceptormediated regulation of L-type Ca2+ currents by L-arginine', Biologicheskie Membrany, vol. 27, no. 5, pp. 440-448.
Nenov, M. N. ; Berezhnov, A. V. ; Fedotova, E. I. ; Grushin, K. S. ; Yu Pimenov, O. ; Murashev, A. N. ; Zinchenko, V. P. ; Kokoz, Yu M. / "Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats : α2-adrenoreceptormediated regulation of L-type Ca2+ currents by L-arginine. In: Biologicheskie Membrany. 2010 ; Vol. 27, No. 5. pp. 440-448.
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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 cGM P-dependent protein kinase (KT5823), dramatically weakened the inhibitory effects of 5 mM ¿-arginine on Ca2+ currents. The agonist of a2-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 ¿-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.",
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T1 - "Arginine paradox" in cardiomyocytes of sprague dawley and spontaneously hypertensive rats

T2 - α2-adrenoreceptormediated regulation of L-type Ca2+ currents by L-arginine

AU - Nenov, M. N.

AU - Berezhnov, A. V.

AU - Fedotova, E. I.

AU - Grushin, K. S.

AU - Yu Pimenov, O.

AU - Murashev, A. N.

AU - Zinchenko, V. P.

AU - Kokoz, Yu M.

PY - 2010

Y1 - 2010

N2 - 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 cGM P-dependent protein kinase (KT5823), dramatically weakened the inhibitory effects of 5 mM ¿-arginine on Ca2+ currents. The agonist of a2-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 ¿-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.

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KW - adrenoceptors

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KW - Cardiomyocytes

KW - L-type ca currents

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