Abstract
Background/Aim. Excitation–contraction coupling is modulated by nitric oxide (NO) which otherwise has either beneficial or detrimental effects on myocardial function during hypoxia-reoxygenation. This work aimed at characterizing the variations of electromechanical delay (EMD) induced by anoxia-reoxygenation within the developing heart and determining whether atrial and ventricular EMD are modulated by NO to the same extent. Methods. Hearts of 4 or 4.5-day-old chick embryos were excised and submitted in vitro to normoxia (45 min), anoxia (30 min) and reoxygenation (60 min). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout experiment. Anoxia-reoxygenation-induced chrono-, dromo- and inotropic disturbances and changes in EMD in atrium (EMDa) and ventricle (EMDv) were investigated in control hearts and in hearts exposed to 0.1, 1, 10, 50 and 100 μM of DETA-NONOate (a NO donating agent) or to 50 μM of L-NAME (a NOS inhibitor). Results. Under normoxia, heart rate, PR interval, ventricular shortening velocity, EMDa and EMDv were similar in control, L-NAME-treated and DETA-NONOate-treated hearts. Under anoxia, cardiac activity became markedly erratic within less than 10 min in all groups. At the onset of reoxygenation, EMDv was increased by about 300% with respect to the preanoxic value while EMDa did not vary significatively. Compared to control conditions, L-NAME or DETA-NONOate had no influence on the negative chrono-, dromo- and inotropic effects induced by anoxia-reoxygenation. However, L-NAME prolonged EMDv during anoxia and delayed EMDv recovery during reoxygenation while 100 μM DETA-NONOate had the opposite effects. EMDa was neither affected by NOS inhibitor nor NO donor. At the end of reoxygenation, all the investigated parameters returned to their basal values. Conclusion. This work provides evidence that a NO-dependent pathway is involved in regulation of the ventricular excitation-contraction coupling in the anoxic-reoxygenated developing heart. (Mol Cell Biochem 265: 141–149, 2004)
Similar content being viewed by others
References
Grabowski CT, Schroeder RE: Atime-lapse photographic study of chick embryos exposed to teratogenic doses of hypoxia. J Embryol Exp Morph 19: 347–362, 1968
Jaffee OC: Hemodynamics and cardiogenesis. The effects of physiologic factors on cardiac development. Birth Defects 14: 393–404, 1978
Ostadal B, Ostadalova I, Dhalla NS: Development of cardiac sensitivity to oxygen deficiency: Comparative and ontogenetic aspects. Physiol Rev 79: 635–659, 1999
Mulder ALM, Van Goor CA, Giussani DA, Blanco CE: Alpha-adrenergic contribution to the cardiovascular response to acute hypox-emia in the chick embryo. Am J Physiol Regul Integr Comp Physiol 281: R2004–R2010, 2001
Raddatz E, Kucera P, de Ribaupierre Y: Response of the embryonic heart to hypoxia and reoxygenation: An in vitro model. Exp Clin Cardiol 2: 128–134, 1997
Meiltz A, Kucera P, de Ribaupierre Y, Raddatz E: Inhibition of bicarbon-ate transport protects embryonic heart against reoxygenation-induced dysfunction. J Mol Cell Cardiol 30: 327–335, 1998
Tenthorey D, de Ribaupierre Y, Kucera P, Raddatz E: Effects of ver-apamil and ryanodine on activity of the embryonic chick heart during anoxia and reoxygenation. J Cardiovasc Pharmacol 31: 195–202, 1998
Sedmera D, Kucera P, Raddatz E: Developmental changes in cardiac recovery from anoxia-reoxygenation. Am J Physiol Regul Integr Comp Physiol 283: R379–R388, 2002
Fantel AG, Mackler B, Stamps LD, Tran TT, Person RE: Reactive oxy-gen species and DNA oxidation in fetal rat tissues. Free Rad Biol Med 25: 95–103, 1998
Louch WE, Ferrier GR, Howlett SE: Changes in excitation-contraction coupling in an isolated ventricular myocyte model of cardiac stunning. Am J Physiol Heart Circ Physiol 283: H800–H810, 2002
Bloch W, Addicks K, Hescheler J, Fleischmann BK: Nitric oxide syn-thase expression and function in embryonic and adult cardiomyocytes. Microsci Res Technol 55: 259–269, 2001
Khan SA, Skaf MW, Harrison RW, Lee K, Minhas KM, Kumar A, Fradley M, Shoukas AA, Berkowitz DE, Hare JM: Nitric oxide reg-ulation of myocardial contractility and calcium cycling. Independent impact of neuronal and endothelial nitric oxide synthases. Circ Res 92: 1322–1329, 2003
Hare JM: Nitric oxide and excitation-contraction coupling. J Mol Cell Cardiol 35: 719–729, 2003
Massion PB, Feron O, Dessy C, Balligand J-L: Nitric oxide and cardiac function. Ten years after, and continuing. Circ Res 93: 388–398, 2003
Weyrich AS, Ma XL, Lefer AM: The role of L-arginine in ameliorating reperfusion injury after myocardial ischemia in the cat. Circulation 86: 279–288, 1992
Depré C, Vanoverschelde J-L, Goudemant J-F, Mottet I, Hue L: Protec-tion against ischemic injury by nonvasoactive concentrations of nitric oxide synthase inhibitors in the perfused rabbit heart. Circulation 92: 1911–1918, 1995
Schlüter KD, Jakob G, Ruiz-Meana M, Garcia-Dorado D, Piper HM: Protection of reoxygenated cardiomyocytes against osmotic fragility by nitric oxide donors. Am J Physiol 271: H428–H434, 1996
Mizuno T, Watanabe M, Sakamoto M, Sunamori M: L-arginine, a nitric oxide precursor, attenuates ischemia-reperfusion injury by inhibition inositol-1,4,5-triphosphate. J Thorac Cardiovasc Surg 115: 931–936, 1998
Xi L, Jarrett NC, Hess ML, Kukreja RC: Myocardial is-chemia/ reperfusion injury in the inducible nitric oxide synthase knockout mice. Life Sci 65: 935–945, 1999
Rouet-Benzineb P, Eddahibi S, Raffestin B, Laplace M, Depond S, Adnot S, Crozatier B: Induction of cardiac nitric oxide synthase 2 in rats exposed to chronic hypoxia. J Mol Cell Cardiol 31: 1697–1708, 1999
Agullo L, Garcia-Dorado D, Inserte J, Paniagua A, Pyrhonen P, Llevadot J, Soler-Soler J: L-arginine limits myocardial cell death secondary to hypoxia-reoxygenation by a cCMP-dependent mechanism. Am J Physiol 276: H1574–H1580, 1999
Shah AM, MacCarthy PA: Paracrine and autocrine effects of nitric oxide on myocardial function. Pharmacol Therap 86: 49–86, 2000
Nakano A, Liu GS, Heusch G, Downey JM, Cohen MV: Exogenous nitric oxide can trigger a preconditioned state through a free radical mechanism, but endogenous nitric oxide is not a trigger of classical ischemic preconditioning. J Mol Cell Cardiol 32: 1159–1167, 2000
Bolli R: Cardioprotective function of inducible nitric oxide synthase and role of nitric oxide in myocardial ischemia and preconditioning: An overview of a decade of research. J Mol Cell Cardiol 33: 1897–1918, 2001
Ignarro LJ, Napoli C, Loscalzo J: Nitric oxide donors and cardiovas-cular agents modulating the bioactivity of nitric oxide-An overview. Circ Res 90: 21–28, 2002
Terrand J, Felley-Bosco E, Courjault-Gautier F, Rochat A-C, Kucera P, Raddatz E: Postanoxic functional recovery of the developing heart is slightly altered by endogenous or exogenous nitric oxide. Mol Cell Biochem 252: 53–63, 2003
Ungureanu-Longrois D, Bézie Y, Perret C, Laurent S: Effects of exogenous and endogenous nitric oxide on the contractile function of cultured chick embryo ventricular myocytes. J Mol Cell Cardiol 29: 677–687, 1997
Shimizu T, Kinugawa K-I, Sugishita Y, Sugishita K, Harada K, Matsui H, Kohmoto O, Serizawa T, Takahashi T: Molecular cloning and expression of inducible nitric oxide synthase in chick embryonic ventricular myocytes. Cardiovasc Res 38: 405–413, 1998
Ji GJ, Fleischmann BK, Bloch W, Feelisch M, Andressen C, Addicks K, Hescheler J: Regulation of the L-type Ca 2 +channel during cardiomyogenesis: Switch from NO to adenylyl cyclase-mediated inhibition. FASEB J 13: 313–324, 1999
Kinugawa K, Takahashi T, Kohmoto O, Yao A, Aoyagi T, Momomura S, Hirata Y, Serizawa T: Nitric oxide-mediated effects of interleukin-6 on [Ca 2 +]i and cell contraction in cultured chick ventricular myocytes. Circ Res 75: 285–295, 1994
Moorman AFM, Schumacher CA, De Boer PAJ, Hagoort J, Bezstarosti K, van den Hoff MJB, Wagenaar GTM, Lamers JMJ, Wuytack F, Christoffels VM, Fiolet JWT: Presence of functional sarcoplasmic reticulum in the developing heart and its confinement to chamber myocardium. Dev Biol 223: 279–290, 2000
Seki S, Nagashima M, Yamada Y, Tsutsuura M, Kobayashi T, Namiki A, Tohse N: Fetal and postnatal development of Ca +transients and Ca +sparks in rat cardiomyocytes. Cardiovasc Res 58: 535–548, 2003
Tibbits GF, Xu LQ, Sedarat F: Ontogeny of excitation-contraction coupling in the mammalian heart. Comp Biochem Physiol A Mol Integr Physiol 132: 691–698, 2002
Romano R, Rochat A-C, Kucera P, de Ribaupierre Y, Raddatz E: Oxidative and glycogenolytic capacities within the developing chick heart. Pediatr Res 49: 363–372, 2001
Lyon X, Kappenberger L, Sedmera D, Rochat A-C, Kucera P, Raddatz E: Pacing redistributes glycogen within the developing myocardium. J Mol Cell Cardiol 33: 513–520, 2001
Moorman AFM, Lamers WH: Molecular anatomy of the developing heart. Trends Cardiovasc Med 4: 257–264, 1994
Franco D, Gallego A, Habets PEMH, Coma VS, Moorman AFM: Species-specific differences of myosin content in the developing cardiac chambers of fish, birds, and mammals. Anat Rec 268: 27–37, 2002
de Jong F, Opthof T, Wilde AAM, Janse MJ, Charles R, Lamers WH, Moorman AFM: Persisting zones of slow impulse conduction in developing chicken hearts. Circ Res 71: 240–250, 1992
Alanis J, Argüello C, Polo L: Effects of heparin on the electrophysi-ological and mechanical properties of early embryonic chick hearts. J Mol Cell Cardiol 29: 2503–2511, 1997
Shrier A, Clay JR: Comparison of the pacemaker properties of chick em-bryonic atrial and ventricular heart cells. J Membr Biol 69: 49–56, 1982
Liang BT: Adenosine receptors and cardiovascular function. Trends Cardiovasc Med 2: 100–108, 1992
Porter GA, Rivkees SA: Ontogeny of humoral heart rate regulation in the embryonic mouse. Am J Physiol Regul Integr Comp Physiol 281: R401–R407, 2001
Maury P, Terrand J, Rosa A, Kucera P, Kappenberger L, Raddatz E: Ventricular but not atrial electro-mechanical delay of the embryonic heart is altered by anoxia-reoxygenation and improved by nitric oxide donor. Basic Res Cardiol 98(3): 191(Abstract), 2003
Hamburger V, Hamilton HL: A series of normal stages in the development of the chick embryo. J Morphol 88: 49–92, 1951
Raddatz E, Servin M, Kucera P: Oxygen uptake during early cardiogenesis of the chick. Am J Physiol 262: H1224–H1230, 1992
Rosa A, Maury J-P, Terrand J, Lyon X, Kucera P, Kappenberger L, Raddatz E: Ectopic pacing at physiological rate improves postanoxic recovery of the developing heart. Am J Physiol Heart Circ Physiol 284: H2384–H2392, 2003
Boucek RJ, Murphy WP, Paff GH: Electrical and mechanical properties of chick embryo heart chambers. Circ Res VII: 787–793, 1959
Raddatz E, Rochat A-C: Heterogeneity of oxidant stress in the reoxy-genated developing heart. J Mol Cell Cardiol 34(6): A52(Abstract), 2002
Hüser J, Wang YG, Sheehan KA, Cifuentes F, Lipsius SL, Blatter LA: Functional coupling between glycolysis and excitation-contraction coupling underlies alternans in cat heart cells. J Physiol 524(3): 795–806, 2000
Brookes PS, Salinas EP, Darley-Usmar K, Eiserich JP, Freeman BA, Darley-Usmar VM, Anderson PG: Concentration-dependent effects of nitric oxide on mitochondrial permeability transition and cytochrome c release. J Biol Chem 275: 20474–20479, 2000
Wink DA, Mitchell JB: Chemical biology of nitric oxide: Insights into regulatory, cytotoxic, and cytoprotective mechanisms of nitric oxide. Free Rad Biol Med 25: 434–456, 1998
Sarre A, Gabioud H, Lange N, Raddatz E: Eur. J. The mitochondrial KATP channel is not involved in the oxidative burst induced by anoxia-reoxygenation in the embryonic heart. Heart Fail 2(1): 90(Abstract), 2003
Gao WD, Liu Y, Marban E: Selective effects of oxygen free radicals on excitation-contraction coupling in ventricular muscle. Implications for the mechanism of stunned myocardium. Circulation 94: 2597–2604, 1996
Wink DA, Vodovotz Y, Grisham MB, DeGraaf W, Cook JC, Pacelli R, Krishna M, Mitchell B: Antioxidant effects of nitric oxide. Meth Enzymol 301: 413–425, 1999
Halliwell B: Antioxidant defense mechanisms. From the beginnig to the end (of the beginning). Free Radic Res 31: 261–272, 1999
Gallo MP, Malan D, Bedendi I, Biasin C, Alloatti G, Levi RC: Regulation of cardiac calcium current by NO and cGMP-modulating agents. Pflugers Arch 441: 621–628, 2001
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Maury, P., Sarre, A., Terrand, J. et al. Ventricular but not atrial electro-mechanical delay of the embryonic heart is altered by anoxia-reoxygenation and improved by nitric oxide. Mol Cell Biochem 265, 141–149 (2004). https://doi.org/10.1023/B:MCBI.0000044391.97857.4d
Issue Date:
DOI: https://doi.org/10.1023/B:MCBI.0000044391.97857.4d