Abstract
The effect of chronic administration of β-guanidinopropionic acid (GPA) on the protein profiling, energy metabolism and right ventricular (RV) function was studied in the rat heart during the weaning and adolescence period. GPA was given in tap water (1–1.5%) using pair drink controls. The feeding of animals with GPA solution for a six week period resulted in elevation of heart to body weight ratio due to body growth retardation. GPA accumulated in the myocardium up to 67.37 ± 5.3 µmoles.g dry weight and the tissue content of total creatine, phosphocreatine and ATP was significantly decreased to 15%, 9% and 65% of control values respectively. Total activity of creatine kinase (CK) was not changed, but the proportion of mitochondrial (Mi) CK isoenzyme was decreased; the percentage of MB isoenzyme of CK was significantly higher. GPA treatment resulted in an elevation of the content of cardiac collagenous proteins and decrease of non-collagenous proteins in the heart; in parallel, a decrease of the collagen I to collagen III ratio was detected. The function of the RV was assessed using an isolated perfused heart with RV performing pressure-volume work. As compared to pair-drink controls, RV function was significantly impaired the GPA group: at any given right atrial filling pressure, the RV systolic pressure and the rate of pressure development were decreased by almost a factor of two. Elevation of the RV diastolic pressure with increasing pulmonary artery diastolic pressure was also significantly steeper in the GPA group which also showed decrease of cardiac output, especially at high outflow resistance. It may be assumed that chronic administration of GPA deeply influenced metabolic parameters, protein profiles and contractile function of the developing heart. On the other hand, concentrations of glucose, total lipids and triglycerides in blood plasma were not affected. All these data confirm the concept that the CK system is of central importance both for heart function and for the regulation of normal growth of cardiac myocytes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Ventura-Clapier R, Veksler V, Hoerter JA: Myofibrillar creatine kinase and cardiac contraction Mol Cell Biochem 133/134: 125–141, 1994
Eppenberger HM: A brief summary of the history of the detection of creatine kinase isoenzyme Mol Cell Biochem 133/134: 9–11, 1994
Zweier JL, Jacobus WE, Korecky B, Brandejs-Barry Y: Bioenergetic consequences of cardiac phosphocreatine depletion induced by creatine analogue feeding. J Biol Chem 266: 2296–20304, 1991
Mekhfi H, Hoerter J, Lauer C, Wisnewsky C, Schwartz K, Ventura-Clapier R: Myocardial adaptation to creatine deficiency in rats fed with β-guanidinopropionic acid, a creatine analogue. Am J Physiol 258: H1151–H1158, 1990
Shoubridge EA, Jeffry FMH, Keogh JM, Radda GK, Seymour AML: Creatine kinase kinetics, ATP turnover and cardiac performance in hearts depleted of creatine with the substrate analogue β-guanidinopropionic acid. Biochim Biophys Acta 847: 25–32, 1985
Shoubridge EA, Radda A: AP nuclear magtnetic resonance study of skeletal muscle metabolism in rats depleted of creatine with analogue β-guanidinopropionic acid. Biochim Biophys Acta 805: 79–88, 1984
Kapelko VI, Kupriyanov W, Novikova NA, Lakomkin VL, Steinshneider AY, Severina MY, Veksler VI, Saks VA: The cardiac contractile failure induced by chronic creatine and phosphocreatine deficiency. J Mol Cell Cardiol 20: 465–479, 1988
Brandejs-Barry Y, Korecky B: Contractile mechanics of papillary muscles of creatine depleted rats. In: VA Saks, YG Bobkov, E Strumia (eds). Creatine phosphate. Biochemistry, pharmacology and clinical efficiency. Edizioni Minerva Medica, Torino, 1987, pp. 58–71
Aliev MK, Saks VA: Quantitative analysis of the phosphocreatine shuttle: A probability approach to the description of phosphocreatine production in the coupled creatine kinase -ATP/ADP translocase-oxidative phosphorylation reactions in heart mitochondria. Biochim Biophys Acta 11:291–300, 1993
Hamman BL, Bittl JA, Jacobus WE, Allen PD, Spencer RS, Tian R, Ingwal JAS: Inhibition of the creatine kinase reaction decreases the contractile reserve of isolated rat hearts. Am J Physiol 269: H1030–H1036, 1995
Anversa P, Ricci R, Olivetti G: Quantitative structural analysis of the myocardium during physiologic growth and induced cardiac hypertrophy: A review. J Am Coll Cardiol 7: 1140–1149, 1986
Pelouch V, Milerová M, Ošt’ádal B, Procházka J: Ontogenetic Development of the Protein Composition of the Right and Left Ventricular Myocardium. In: V Ježek, M Morpurgo, R Tramar (eds). Right Ventricular Hypertrophy and Function in Chronic Lung Disease. Springer Verlag, Berlin, 1992, pp. 39–54
Pelouch V, Ošt’ádal B, Kolář F, Milerová J, Grünermel J: Chronic hypoxia-induced right ventricular enlargement, age dependent changes of collagenous and non-collagenous cardiac protein fractions. In: B Ošt’ádal, NS Dhalla, (eds). Heart Function in Health and Disease. Kluwer Academic Publishers, Boston, 1993, pp. 209–218
Pelouch V, Dixon IMC, Golfman L, Beamish RE, Dhalla NS: Role of extracellular matrix proteins in heart function. Mol Cell Biochem, 129: 101–120, 1994
Sugden PH, Fuller SJ: Correlations between cardiac protein synthesis rates, intracellular pH and the concentrations of creatine metabolites. Biochem J 273: 339–346, 1991
Sugga H: Ventricular energetics. Physiol Rev 70: 247–277, 1990
Mast F, Elzinga G: Oxidative and glycolytic ATP formation of rabbit papillary muscle in oxygen and nitrogen. Am J Physiol, 258: H1144–H1150, 1990
Lopaschuk GD, Spafford MA: Energy substrate utilization by isolated working hearts from newborn rabbits. Am J Physiol 258: H1274–H1280, 1990
Hoerter JA, Ventura-Clapier R, Kuznetsov A: Compartmentation of creatine kinases during perinatal development of mammalian heart. Mol Cell Biochem 133/134: 277–286, 1994
Pelouch V, Milerová M, Ošt’ádal B: Effect of low concentration of creatinephosphate (CP) on protein composition of the rat myocardium. Physiol Res 40: 614, 1991
Pelouch V, Milerová M. Ošt’ádal B, Šamánek M, Hučín B: Protein profiling of human atrial and ventricular musculature: The effect of normoxaemia and hypoxaemia in congenital heart diseases. Physiol Res 42:235–242, 1993
Pelouch V, Dixon IMC, Sethi R, Dhalla NS: Alteration of collagenous profile in congestive heart failure secondary to myocardial infarction. Mol Cell Biochem 129: 121–131, 1994
Pelouch V, Milerová M, Ošt’ádal B, Hučín B, Šamánek M: Differences between atrial and ventricular protein profiling in children with congenital heart disease. Mol Cell Biochem 147: 49, 1995
Lowry OH, Rosenbrough HJ, Fair AL, Randall RJ: Protein measurement with Folin phenol reagent. J Biol Chem 193: 265–275, 1951
Pelouch V: Molecular aspects of regulation of cardiac contraction. Physiol Res 44: 53–61, 1995
Černohorský J, Pelouch V, Milerová M, Ošt’ádal B: Protein profiling of the myocardium exposed to pressure overload from birth. Physiol Res 44: 139–142, 1995
Bergmeyer HU: In: HU Bergmeyer (ed.) Methods of Enzymatic Analysis. Academic Press, New York 1964, pp 1777–1785
De Saedeleer M, Marechal G: Chemical energy usage during isometric twitches of frog sartorius muscle intoxicated with an isomere of creatine, β-guanidinopropionate. Pflügers Arch 402: 185–189, 1984
Kolář F, Ošt’ádal B: Right ventricular function in rats with hypoxic pulmonary hypertension. Pflügers Arch 419: 121–126, 1991
Papoušek F, Kolář F, Ošt’ádal B, Přibík V: Microcomputer analysis of the intraventricular pressure curve of the isolated rat heart. Physiol Bohemosl 38: 473–476, 1989
Eppenberger-Eberhardt M, Riesinger I, Messerli M, Schwarb P, Muller M, Eppenberger HM, Wallimann T: Adult rat cardiomyocytes cultured in creatine-deficient medium display large mitochondria with paracrystalline inclusions, enriched for creatine kinase. J Cell Biol 113:289–302, 1991
Ingwall JS, Kramer MF, Fifer MA, Lorell BH, Shemin R, Grossman W, Allen PD: The creatine kinase system in normal and diseased human myocardium. N Engl J Med 313: 1050–1054, 1985
Fontanet HL, Trask RV, Haas RC, Strauss AW, Abendschien DR, Billadello JJ: Regulation of expression of M, B, and mitochondrial creatine kinase mRNAs in the left ventricle after pressure overload in rats. Circ Res 68: 1007–1012, 1991
Bugaisky LB, Gupta M, Gupta MP, Zak R: Cellular and molecular mechanisms of cardiac hypertrophy. In: Fozard et al. (eds). The Heart and Cardiovascular System, II Edition. Raven Press, New York. 1992, pp 1621–1640
Bass A, Šamánek M, Ošt’ádal B, Hučín B, Stejskalová M, Pelouch V: Differences between atria and ventricular energy supplying enzymes in children. J App Cardiol 3: 397–405, 1988
Weber KT: Cardiac interstitium: extracellular space of the myocardium. In: HA fozzard (ed.) The Heart and Cardiovascular System. Second edition. Raven Press Ltd., New York, 1992, pp. 1465–1480
Honda M, Yamada S, Goto Y, Ishikawa S, Yoshilaner H, Ishinaga Y, Kuzuo H, Morioka S, Moriayma K: Biochemical and structural remodeling of collagen in the right ventricular hypertrophy induced by monocrotaline. Jap Circ J 56: 392–403, 1992
Saks VA, Khuchua ZA, Vasilyeva EV, Belikova OY, Kuznetsov AV: Metabolic compartmentation and substrate channelling in muscle cells. Role of coupled creatine kinases in in vitro regulation of cellular respiration — a synthesis. Mol Cell Biochem 133/134: 155–192, 1994
Dowell RT: Phosphorylcreatine shuttle enzymes during perinatal heart development. Biochemical Med and Metabol Biol 37: 374–388, 1987
Wright G, Kingston MA, Ross IS: Role of metabolic acidosis on cardiac mechanical performance during severe acute hypoxia and reoxygenation is small and transient. Cardiovasc Res 29: 611–615, 1995
Wyss M, Wallimann T: Creatine metabolism and the consequences of creatine depletion in muscle. Mol Cell Biochem 133/134: 51–68, 1994
Hoerter JA, Lauer C, Vassort G, Gueron M: Sustained function of normoxemic hearts depleted in ATP and phosphocreatine: a P-NMR study. Am J Physiol 255: C192–C201, 1988
Bessman SP, Carpenter CL: The creatine-creatine phosphate energy shutle. Ann Rev Biochem 54: 831–862, 1985
Lompre AM, Mercadier JJ, Schwartz K: Changes in gene expression during cardiac growth. Intern Rev Cytol 124: 137–186, 1991
Seppet EK, Saks VA: Thyroid hormones and the creatine kinase system in cardiac cells. Mol Cell Biochem 133/134: 299–309, 1994
Gudbiarnason S, Mathes P, Ravens KG: Functional compartmentation of ATP and creatine phosphate in heart muscle. J Mol Cell Cardiol 1: 325–339, 1970
Ventura-Clapier R: Myocardial adaptation to creatine deficiency in rats fed with β-guanidinopropionic acid, a creatine anologue. Am J Physiol 258: H1151–H1158, 1990
Jacobus, WE: Respiratory control and integration of heart high energy phosphate metabolism by mitochondrial creatine kinase. Ann Rev Physiol 47: 707–25, 1985
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1996 Kluwer Academic Publishers
About this chapter
Cite this chapter
Pelouch, V. et al. (1996). Cardiac phosphocreatine deficiency induced by GPA during postnatal development in rat. In: Vetter, R., Krause, EG. (eds) Biochemical Regulation of Myocardium. Developments in Molecular and Cellular Biochemistry, vol 19. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-1289-5_8
Download citation
DOI: https://doi.org/10.1007/978-1-4613-1289-5_8
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4612-8551-9
Online ISBN: 978-1-4613-1289-5
eBook Packages: Springer Book Archive