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Intrinsic cardiac adrenergic (ICA) cell density and MAO-A activity in failing rat hearts

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Abstract

The efficiency (work/oxygen consumption) of isolated papillary muscles from failing hearts is reduced. We investigated whether this can be due to an increase of intrinsic cardiac adrenergic (ICA) cell density. The number of ICA cells in the septum and both ventricular walls was determined by tyrosine hydroxylase immunohistochemistry in rats with monocrotaline-induced pulmonary hypertension. We found that the number of ICA cells is about 200,000 per rat heart. ICA cell density was significantly lower in right ventricular myocardium of hypertrophied hearts (P < 0.01). MAO-A enzyme histochemistry and inhibition experiments with clorgyline in papillary muscles were performed to localize the enzyme and to determine its oxygen consumption. Upregulation of MAO-A was found in the right ventricular wall and papillary muscles of failing hearts (P = 0.018). A positive correlation between ICA cell density and MAO-A activity was absent. Clorgyline (2 μM) decreased the basal rate of oxygen consumption of right ventricular papillary muscles by 65 μM O2/s (P = 0.027). This rate can only be maintained for several seconds judging from the catecholamine content of the preparations reported previously. High ICA cell activity rather than density and/or recycling of oxidized catecholamines are discussed as alternative explanations for the low myocardial efficiency in experimental pulmonary hypertension.

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References

  • Bogaards SJP, Vaz FM, Schalij I, van Groen D, van der Laarse WJ (2014) MAO-A inhibition reduces basal oxygen consumption and restores isoprenaline sensitivity of hypertrophied rat papillary muscle in vitro. J Muscle Res Cell Motil 8:69

    Google Scholar 

  • Braunwald E, Chidsey CA, Harrison MD, Gaffney TE, Kahler RL (1963) Studies on the function of the adrenergic nerve endings in the heart. Circulation 28:958–969

    Article  CAS  PubMed  Google Scholar 

  • Decking UKM (2002) Spatial heterogeneity in the heart: recent insights and open questions. Am Physiol Soc 17(6):246–250. doi:10.1152/nips.01393.2002

    Google Scholar 

  • Ebert SN, Taylor DG (2006) Catecholamines and development of cardiac pacemaking: an intrinsically intimate relationship. Cardiovasc Res 72(3):364–374. doi:10.1016/j.cardiores.2006.08.013

    Article  CAS  PubMed  Google Scholar 

  • Frederiks WM, Marx F (1985) Quantitative aspects of the histochemical tetrazolium salt reaction on monoamine oxidase activity in rat liver. Histochem J 17(6):707–715. doi:10.1007/BF01003522

    Article  CAS  PubMed  Google Scholar 

  • Gibbs CL (1978) Cardiac energetics. Physiol Rev 58(1):174–254

    CAS  PubMed  Google Scholar 

  • Giménez-Xavier P, Gómez-Santos C, Castaño E, Francisco R, Boada J, Unzeta M, Sanz E, Ambrosio S (2006) The decrease of NAD(P)H has a prominant role in dopamine toxicity. Biochem Biophys Acta 1762:564–574. doi:10.1016/j.bbadis.2006.02.003

    PubMed  Google Scholar 

  • Handoko ML, de Man FS, Happé CM, Schalij I, Musters RJP, Westerhof N, Postmus PE, Paulus WJ, van der Laarse WJ, Vonk-Noordegraaf A (2009) Opposite effects of training in rats with stable and progressive pulmonary hypertension. Circulation 120:42–49. doi:10.1161/CIRCULATIONAHA.108.829713

    Article  CAS  PubMed  Google Scholar 

  • Huang MH, Friend DS, Sunday ME, Singh K, Haley K, Austen KF, Kelly RA, Smith TW (1996) An intrinsic adrenergic system in mammalian heart. J Clin Invest 98(6):1298–1303. doi:10.1172/JCI118916

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Huang MH, Bahl JJ, Wu Y, Hu F, Larson DF, Roeske WR, Ewy GA (2005) Neuroendocrine properties of intrinsic cardiac adrenergic cells in fetal rat heart. Am J Physiol Heart Circ Physiol 288:H497–H503. doi:10.1152/ajpheart.00591.2004

    Article  CAS  PubMed  Google Scholar 

  • Kaludercic N, Takimoto E, Nagayama T, Feng N, Lai EW, Bedja D, Chen K, Gabrielson KL, Blakely RD, Shih JC, Pacak C, Kass DA, Di Lisa F, Paolocci N (2010) Monoamine oxidase A-mediated enhanced catabolism of norepinephrine contributes to adverse remodeling and pump failure in hearts with pressure overload. Circ Res 106:193–202. doi:10.1161/CIRCRESAHA.109.198366

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kaludercic N, Carpi A, Menabò R, Di Lisa F, Paolocci N (2011) Monoamine oxidases (MAO) in the pathogenesis of heart failure and ischemia/reperfusion injury. Biochem Biophys Acta 7:1323–1332. doi:10.1016/j.bbamcr.2010.09.010

    Article  Google Scholar 

  • Kaludercic N, Carpi A, Nagayama T, Sivakumaran V, Zhu G, Lai EW, Bedja D, De Mario A, Chen K, Gabrielson KL, Lindsey ML, Pacak K, Takimoto E, shih JC, Kass DA, Di Lisa F, Paolocci N (2013) Monoamine oxidase B prompts mitochondrial and cardiac dysfunction in pressure overloaded hearts. Antioxid Redox Signal (In press). Doi 10.1089/ars.2012.4616

  • Kaye DM, Lefkovits J, Cox H, Lambert G, Jennings G, Turner A, Esler MD (1995) Regional epinephrine kinetics in human heart failure: evidence for extra-adrenal nonneuronal release. Am J Physiol Heart Circ Physiol 269(1):182–188

    Google Scholar 

  • Kimura K, Ieda M, Kanazawa H, Yagi T, Tsunoda M, Ninomiya S, Kurosawa H, Yoshimi K, Mochizuki H, Yamazaki K, Ogawa S, Fukuda K (2007) Cardiac sympathetic rejuvenation. A link between nerve function and cardiac hypertrophy. Circ Res 100:1755–1764. doi:10.1161/01.RES.0000269828.62250.ab

    Article  CAS  PubMed  Google Scholar 

  • Knaapen P, Germans T, Knuuti J, Paulus WJ, Dijkmans PA, Allaart CP, Lammertsma AA, Visser FC (2007) Myocardial energetics and efficiency: current status of the noninvasive approach. Circulation 115:918–927. doi:10.1161/CICULATIONAHA.106.660639

    Article  PubMed  Google Scholar 

  • Layland J, Kentish JC (2000) Effects of α −1 or β stimulation on work-loop and isometric contractions of isolated rat cardiac trabeculae. J Physiol 524(1):205–219. doi:10.1111/j.1469-7793.2000.t01-1-00205.x

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lee-de Groot MBE, des Tombe AL, van der Laarse WJ (1998) Calibrated histochemistry of myoglobin concentration in cardiomyocytes. J Histochem Cytochem 46(9):1077–1084. doi:10.1177/002215549804600912

    Article  CAS  PubMed  Google Scholar 

  • Leineweber K, Seyfarth T, Abraham G, Gergershagen H-P, Heinroth-Hoffmann I, Pönicke K, Brodde O-E (2003) Cardiac β receptor changes in monocrotaline-treated rats: differences between membrane preparations from whole ventricles and isolated cardiomyocytes. J Cardiovasc Pharmacol 41(3):333–342

    Article  CAS  PubMed  Google Scholar 

  • Markhasin VS, Solovyova O, Katsnelson LB, Protsenko Yu, Kohl P, Noble D (2003) Mechano–electric interactions in heterogeneous myocardium: development of fundamental experimental and theoretical models. Prog Biophys Mol Biol 82(1–3):207–220. doi:10.1016/S0079-6107(03)00017-8

    Article  CAS  PubMed  Google Scholar 

  • Minami M, Yasuda H, Yamazaki N, Kojima S, Nishijima H, Matsumura N, Togashi H, Koike Y, Saito H (1983) Plasma norepinephrine concentration and plasma dopamine-beta-hydroxylase activity in patients with congestive heart failure. Circulation 67:1324–1329. doi:10.1161/01.CIR.67.6.1324

    Article  CAS  PubMed  Google Scholar 

  • Ruiter G, Wong YY, de Man FS, Handoko ML, Jaspers RT, Postmus PE, Westerhof N, Niessen HWM, van der Laarse WJ, Vonk Noordegraaf A (2013) Right ventricular oxygen supply parameters are decreased in human and experimental pulmonary hypertension. J Heart Lung Transpl 32:231–240. doi:10.1016/j.healun.2012.09.025

    Article  Google Scholar 

  • Saygili E, Günzel C, Saygili E, Noor-Ebad F, Schwinger RHG, Mischke K, Marx N, Schauerte P, Rana OR (2011) Irregular electrical activation of intrinsic cardiac adrenergic cells increases catecholamine-synthesizing enzymes. Biochem Biophys Res Commun 413(3):432–435. doi:10.1016/j.bbrc.2011.08.113

    Article  CAS  PubMed  Google Scholar 

  • Thomas JA, Marks BH (1978) Plasma norepinephrine in congestive heart failure. Am J Cardiol 41(2):233–243. doi:10.1016/0002-9149(78)90162-5

    Article  CAS  PubMed  Google Scholar 

  • van Beek-Harmsen BJ, van der Laarse WJ (2005) Immunochemical determination of cytosolic cytochrome c concentration in cardiomyocytes. J Histochem Cytochem 53(7):803–807. doi:10.1369/jhc.4C6527.2005

    Article  PubMed  Google Scholar 

  • van der Laarse WJ, des Tombe AL, van Beek-Harmsen BJ, Lee-de Groot MBE, Jaspers RT (2005) Krogh’s diffusion coefficient for oxygen in isolated Xenopus skeletal muscle fibers an rat myocardial trabeculae at maximim rates of oxygen consumption. J Appl Physiol 99(6):2173–2180. doi:10.1152/japplphysiol.00470.2005

    Article  PubMed  Google Scholar 

  • Vescovo G, Jones SM, Harding SE, Poole-Wilson PA (1989) Isoproterenol sensitivity of isolated cardiac myocytes from Rats with monocrotaline-induced right-sided hypertrophy and heart failure. J Mol Cell Cardiol 21(10):1047–1061. doi:10.1016/0022-2828(89)90803-1

    Article  CAS  PubMed  Google Scholar 

  • Villeneuve C, Guilbeau-Frugier C, Sicard P, Lairez O, Ordener C, Duparc T, De Paulis D, Couderc B, Spreux-Varoquaux O, Tortosa F, Garnier A, Knauf C, Valet P, Borchi E, Nediani C, Gharib A, Ovize M, Delisle M-B, Parini A, Mialet-Perez J (2013) p53-PGC-1a pathway mediates oxidative mitochondrial damage and cardiomyocyte necrosis induced by Monoamine oxidase-A upregulation: role in chronic left ventricular dysfunction in mice. Antioxid Redox Signal 18(1):5–18. doi:10.1089/ars.2011.4373

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wong YY, Handoko ML, Mouchaers KTB, de Man FS, Vonk Noordegraaf A, van der Laarse WJ (2010) Reduced mechanical efficiency of rat papillary muscle related to degree of hypertrophy of cardiomyocytes. Am J Physiol Heart Circ Physiol 298:H1190–H1197. doi:10.1152//ajpheart.00773.2009

    Article  CAS  PubMed  Google Scholar 

  • Wong YY, Ruiter G, Lubberink M, Raijmakers PG, Knaapen P, Marcus JT, Boonstra A, Lammertsma AA, Westerhof N, van der Laarse WJ, Vonk-Noordegraaf A (2011) Right ventricular failure in idiopathic pulmonary arterial hypertension is associated with inefficient myocardial oxygen utilization. Circ Heart Fail 4:700–706. doi:10.1161/CIRCHEARTFAILURE.111.962381

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

We thank I. Schalij and P. Sneekes for expert technical assistance.

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Authors and Affiliations

  1. Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, Van der Boechorststraat 7, 1081 BT, Amsterdam, The Netherlands

    Vincent W. W. van Eif, Sylvia J. P. Bogaards & Willem J. van der Laarse

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  1. Vincent W. W. van Eif
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  2. Sylvia J. P. Bogaards
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  3. Willem J. van der Laarse
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Correspondence to Willem J. van der Laarse.

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van Eif, V.W.W., Bogaards, S.J.P. & van der Laarse, W.J. Intrinsic cardiac adrenergic (ICA) cell density and MAO-A activity in failing rat hearts. J Muscle Res Cell Motil 35, 47–53 (2014). https://doi.org/10.1007/s10974-013-9373-6

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