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Cardiovascular & Hematological Disorders-Drug Targets

Editor-in-Chief

ISSN (Print): 1871-529X
ISSN (Online): 2212-4063

A Pilot Study to Assess Adenosine 5’-triphosphate Metabolism in Red Blood Cells as a Drug Target for Potential Cardiovascular Protection

Author(s): Pollen K.F. Yeung, Jodi Tinkel and Dena Seeto

Volume 15, Issue 3, 2015

Page: [224 - 232] Pages: 9

DOI: 10.2174/1871529X15666151102102702

Abstract

Objective: To study the effect of exercise preconditioning on adenosine 5’triphosphate (ATP) metabolism in red blood cells and cardiovascular protection against injury induced by isoproterenol in vivo.

Methods: Male Sprague Dawley rats (SDR) were each exercised on a treadmill for 15 minutes at 10 m/min and 10% grade (n = 7) (LowEx), or 14 m/min and 22% grade (n = 8) (VigEx). Two hours after the exercise, each rat received a single dose of isoproterenol (30 mg/kg) by subcutaneous (sc) injection. Two separate groups of SDR were used as control: One received no exercise (n = 10) (NoEx) and the other received no exercise and no isoproterenol (n = 11) (NoIso). Serial blood samples were collected over 5 hours for measurement of ATP and its catabolites by a validated HPLC. Hemodynamic recording was collected continuously for the duration of the experiment. Data were analysed using ANOVA and t-tests and difference considered significant at p < 0.05.

Results: Exercise pre-conditioning (both LowEx and VigEx) reduced mortality after isoproterenol from 50% to < 30% (p > 0.05). It attenuated the rebound in blood pressure significantly (p < 0.05 between NoEx vs VigEx), attenuated the increase of RBC adenosine 5’-monophosphate (AMP) concentrations induced by isoproterenol, and also decreased the breakdown of ATP to AMP in the RBC ( p < 0.05 vs NoEx).

Conclusion: Exercise pre-conditioning decreased the blood pressure rebound and also breakdown of ATP in RBC after isoproterenol which may be exploited further as a drug target for cardiovascular protection and prevention.

Keywords: ATP, cardiovascular protection, exercise preconditioning, hemodynamic, RBC, target, toxicity, rats.

Graphical Abstract

[1]
Olsson, R.; Pearson, J. Cardiovascular purinoceptors. Physiol. Rev., 1990, 70761-70845.
[2]
Burnstock, G. Purinergic signaling and vascular cell proliferation and death. Arterioscler. Thromb. Vasc. Biol., 2002, 22(3), 364-373.
[3]
Ingwall, J.S. Energy metabolism in heart failure and remodelling. Cardiovasc. Res., 2009, 81(3), 412-419.
[4]
Laubach, V.E.; French, B.A.; Okusa, M.D. Targeting of adenosine receptors in ischemia-reperfusion injury. Expert Opin. Ther. Targets, 2011, 15(1), 103-118.
[5]
Yang, X.; Cohen, M.V.; Downey, J.M. Mechanism of cardioprotection by early ischemic preconditioning. Cardiovasc. Drugs Ther., 2010, 24(3), 225-234.
[6]
Berne, R. The role of adenosine in the regulation of coronary blood flow. Circ. Res., 1980, 47807-47813.
[7]
Gerlach, E.; Becker, B.F.; Nees, S. The Topic and Perspectives in Adenosine Research; Gerlach, E.; Becker, B. F.; Springer-Verlag: New York NY, . , 1987, pp. 309-320.
[8]
Cohen, M.V.; Downey, J.M. Adenosine: trigger and mediator of cardioprotection. Basic Res. Cardiol., 2008, 103(3), 203-215.
[9]
Burnstock, G. Purines and sensory nerves. Handb. Exp. Pharmacol., 2009, 194, 333-392.
[10]
McCallion, K.; Harkin, D.W.; Gardiner, K.R. Role of adenosine in immunomodulation: review of the literature. Crit. Care Med., 2004, 32(1), 273-277.
[11]
Gomes, C.V.; Kaster, M.P.; Tome, A.R.; Agostinho, P.M.; Cunha, R.A. Adenosine receptors and brain diseases: neuroprotection and neurodegeneration. Biochim. Biophys. Acta, 2011, 1808(5), 1380-1399.
[12]
Donato, M.; Gelpi, R.J. Adenosine and cardioprotection during reperfusion--an overview. Mol. Cell. Biochem., 2003, 251(1-2), 153-159.
[13]
Das, M.; Das, D.K. Molecular mechanism of preconditioning. IUBMB Life, 2008, 60(4), 199-203.
[14]
Bein, B.; Meybohm, P. Organ protection by conditioning. Anasthesiol. Intensivmed. Notfallmed. Schmerzther., 2010, 45(4), 254-261. quiz 262.
[15]
Porkka-Heiskanen, T.; Kalinchuk, A.; Alanko, L.; Urrila, A.; Stenberg, D. Adenosine, energy metabolism, and sleep. ScientificWorldJournal, 2003, 3, 790-798.
[16]
Tykarski, A.; Gluszek, J.; Banaszak, F. Value of oxypurines and uric acid in plasma, renal excretion of oxypurines and uric acid as well as plasma adenosine deaminase and AMP deaminase activity with essential hypertension.(in Polish). Pol. Arch. Med. Wewn., 1993, 89223-89229.
[17]
Duthie, G.; Beattie, J.; Arthur, J.; Franklin, M.; Morrice, P.; James, W. Blood antioxidants and indices of lipid peroxidation in subjects with angina pectoris. Nutrition, 1994, 10313-10316.
[18]
Yeung, P.; Buckley, S.; Hung, O.; Pollak, P.; Barclay, K.; Feng, J.; Klassen, G. Effect of diltiazem on plasma concentrations of oxypurines and uric acid. Therap. Drug Monit., 1997, 19286-19291.
[19]
Funaya, H.; Kitakaze, M.; Node, K.; Minamino, T.; Komamura, K.; Hori, M. Plasma adenosine levels increase in patients with chronic heart failure. Circulation, 1997, 95(6), 1363-1365.
[20]
Kitakaze, M.; Minamino, T.; Node, K.; Koretsune, Y.; Komamura, K.; Funaya, H.; Kuzuya, T.; Hori, M. Elevation of plasma adenosine levels may attenuate the severity of chronic heart failure. Cardiovasc. Drugs Ther., 1998, 12(3), 307-309.
[21]
Taddei, S.; Virdis, A.; Favilla, S.; Salvetti, A. Adenosine activates a vascular renin-angiotensin system in hypertensive subjects. Hypertens., 1992, 19(6 Pt 2), 672-675.
[22]
Franco, M.; Perez-Mendez, O.; Martinez, F. Interaction of intrarenal adenosine and angiotensin II in kidney vascular resistance. Curr. Opin. Nephrol. Hypertens., 2009, 18(1), 63-67.
[23]
Tang, E.H.; Vanhoutte, P.M. Endothelial dysfunction: a strategic target in the treatment of hypertension? Pflugers Arch., 2010, 459(6), 995-1004.
[24]
DeJong, J.W. Martinus Nijhoff Publisher: Boston, U.S.A.,, 1988.
[25]
Round, S.; Hsieh, L.; Agarwal, K. Effects of endotoxin injury on endothelial cell adenosine metabolism. J. Lab. Clin. Med., 1994, 123309-123317.
[26]
Yeung, P. ATP Metabolism as Biomarker Target for Cardiovascular Protection (Editorial). Cardiol. Pharmacol., 2013, 2(e), 118.
[27]
Yeung, P.; Feng, J. Potential surrogate markers for pharmacodynamics of diltiazem: RBC concentrations of adenosine and adenine nucleotides. Pharm. Sci. Supple., 1998, (1), S-329.
[28]
Yeung, P.; Dauphinee, J.; Simonson, K.; Gouzoules, T. RBC concentrations of ATP as potential in vivo biomarkers for cardiovascular safety of anti-hypertensive agents in rats. Clin. Pharmacol. Ther., 2009, 85(1)PIII-8. , S70.
[29]
Yeung, P.; Xu, Z.; Seeto, D. Diltiazem Reduces Mortality and Breakdown of ATP in Red Blood Cell Induced by Isoproterenol in a Freely Moving Rat Model in vivo . Metabolites, 2014, 4(Online), 775-789.
[30]
Marongiu, E.; Crisafulli, A. Cardioprotection acquired through exercise: the role of ischemic preconditioning. Curr. Cardiol. Rev., 2014, 10(4), 336-348.
[31]
Powers, S.K.; Smuder, A.J.; Kavazis, A.N.; Quindry, J.C. Mechanisms of exercise-induced cardioprotection. Physiology (Bethesda), 2014, 29(1), 27-38.
[32]
Shen, Y.J.; Pan, S.S.; Zhuang, T.; Wang, F.J. Exercise preconditioning initiates late cardioprotection against isoproterenol-induced myocardial injury in rats independent of protein kinase C. J. Physiol. Sci., 2011, 61(1), 13-21.
[33]
Silva, J.A., Jr; Santana, E.T.; Manchini, M.T.; Antonio, E.L.; Bocalini, D.S.; Krieger, J.E.; Tucci, P.J.; Serra, A.J. Exercise training can prevent cardiac hypertrophy induced by sympathetic hyperactivity with modulation of kallikrein-kinin pathway and angiogenesis. PLoS One, 2014, 9(3)e91017
[34]
Hydock, D.S.; Lien, C.Y.; Jensen, B.T.; Schneider, C.M.; Hayward, R. Exercise preconditioning provides long-term protection against early chronic doxorubicin cardiotoxicity. Integr. Cancer Ther., 2011, 10(1), 47-57.
[35]
Yeung, P.K.; Dauphinee, J.; Gouzoules, T.; Simonson, K.; Schindler, C. Exercise improves hemodynamic profiles and increases red blood cell concentrations of purine nucleotides in a rodent model. Ther. Adv. Cardiovasc. Dis., 2010, 4(6), 341-347.
[36]
Yeung, P.; Dauphinee, J.; Marcoux, T. Effect of acute exercise on cardiovascular hemodynamic and red blood cell concentrations of purine nucleotides in hypertensive compared with normotensives rats. Ther. Adv. Cardiovasc. Dis., 2013, 7(2), 63-74.
[37]
Yeung, P.; Seeto, D. A study of the effect of isoproterenol on red blood cell concentrations of adenine nucleotides in a freely moving rat model in vivo. Cardiovas. Pharmacol., 2013, 2(1), 102. [on-Line].
[38]
Yeung, P.; Ding, L.; Casley, W. HPLC assay with UV detection for determination of RBC purine nucleotides concentrations and application for biomarker study in vivo. J. Pharm. Biomed. Anal., 2008, 47(2), 377-382.
[39]
Dudzinska, W.; Lubkowska, A.; Dolegowska, B.; Safranow, K.; Jakubowska, K. Adenine, guanine and pyridine nucleotides in blood during physical exercise and restitution in healthy subjects. Eur. J. Appl. Physiol., 2010, 110(6), 1155-1162.
[40]
Rankin, A.J.; Rankin, A.C.; MacIntyre, P.; Hillis, W.S. Walk or run? Is high-intensity exercise more effective than moderate-intensity exercise at reducing cardiovascular risk? Scott. Med. J., 2012, 57(2), 99-102.
[41]
Lee, S.K.; Kim, C.S.; Kim, H.S.; Cho, E.J.; Joo, H.K.; Lee, J.Y.; Lee, E.J.; Park, J.B.; Jeon, B.H. Endothelial nitric oxide synthase activation contributes to post-exercise hypotension in spontaneously hypertensive rats. Biochem. Biophys. Res. Commun., 2009, 382(4), 711-714.
[42]
Wan, W.; Powers, A.S.; Li, J.; Ji, L.; Erikson, J.M.; Zhang, J.Q. Effect of post-myocardial infarction exercise training on the renin-angiotensin-aldosterone system and cardiac function. Am. J. Med. Sci., 2007, 334(4), 265-273.
[43]
Xu, X.; Wan, W.; Ji, L.; Lao, S.; Powers, A.S.; Zhao, W.; Erikson, J.M.; Zhang, J.Q. Exercise training combined with angiotensin II receptor blockade limits post-infarct ventricular remodelling in rats. Cardiovasc. Res., 2008, 78(3), 523-532.
[44]
Lizardo, J.H.; Silveira, E.A.; Vassallo, D.V.; Oliveira, E.M. Post-resistance exercise hypotension in spontaneously hypertensive rats is mediated by nitric oxide. Clin. Exp. Pharmacol. Physiol., 2008, 35(7), 782-787.
[45]
Dudzinska, W.; Lubkowska, A.; Dolegowska, B.; Suska, M.; Janiak, M. Uridine - an indicator of post-exercise uric acid concentration and blood pressure. Physiol. Res., 2015, 64(4), 467-477.
[46]
Halliwill, J.; Buck, T.; Lacewell, A.; Romero, S. Post-exercise hypotension and sustained post-exercise vasodilation: What happens after we exercise? Exp. Physiol., 2013, 98(1), 7-18.
[47]
Ascensao, A.; Lumini-Oliveira, J.; Oliveira, P.J.; Magalhaes, J. Mitochondria as a target for exercise-induced cardioprotection. Curr. Drug Targets, 2011, 12(6), 860-871.
[48]
Bergfeld, G. R.; Forrester, T. Release of ATP from human erythrocytes in response to a brief period of hypoxia and hypercapnia. Cardiovas. Res., 1992, 2640-2647.
[49]
Watts, J.A. Protection of ischemic hearts by Ca2+ antagonists. J. Mol. Cell. Cardiol., 1986, 18(1), 71-75.
[50]
Ellsworth, M.L. The red blood cell as an oxygen sensor: what is the evidence? Acta Physiol. Scand., 2000, 168(4), 551-559.
[51]
Jensen, F.B. The dual roles of red blood cells in tissue oxygen delivery: oxygen carriers and regulators of local blood flow. J. Exp. Biol., 2009, 212(Pt 21), 3387-3393.
[52]
Lopez-Barneo, J.; Nurse, C.A.; Nilsson, G.E.; Buck, L.T.; Gassmann, M.; Bogdanova, A.Y. First aid kit for hypoxic survival: sensors and strategies. Physiol. Biochem. Zool., 2010, 83(5), 753-763.
[53]
Kolathuru, S.; Yeung, P. Therapeutic Potential of Adenosine Transport Modulators for Cardiovascular Protection (Editorial). Cardiol. Pharmacol., 2015, 4(3)

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