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Activity Induced by a Naphthalene-Prazosin Derivative on Ischemia/Reperfusion Injury in Rats

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DOI: 10.4236/pp.2014.512123    3,605 Downloads   4,150 Views   Citations


In this study, a new naphthalene-prazosin derivative (compound 5) was synthetized with the objective of evaluating its activity on ischemia/reperfusion injury. The Langendorff technique was used to evaluate the effect of the compound 5 on ischemia/reperfusion injury. Additionally, the mechanism of action involved in the activity exerted by the compound 5 on perfusion pressure and coronary resistance was evaluated by measuring left ventricular pressure in absence or presence of following compounds; prazosin, metoprolol, indomethacin and nifedipine. The results showed that the compound 5 reduced infarct size compared with the control conditions. Other results showed that the compound 5 significantly increases (p = 0.05) the perfusion pressure and coronary resistance in isolated rat heart. In addition, other data indicate that the compound 5 increases left ventricular pressure in a dose-dependent manner (0.001 to 100 nM); however, this phenomenon was significantly inhibited by nifedipine at a dose of 1 nM (p = 0.05) and this effect was independent of cAMP levels. In conclusion, these data suggest that the naphthalene-prazosin derivative exerts a cardio protective effect via the calcium channels activation and consequently induces changes in the left ventricular pressure levels. This phenomenon results in a decrease of myocardial necrosis after ischemia and reperfusion.

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The authors declare no conflicts of interest.

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Sarabia-Alcocer, B. , Figueroa-Valverde, L. , Díaz-Cedillo, F. , Hau-Heredia, L. , Rosas-Nexticapa, M. , García-Cervera, E. , Pool-Gómez, E. , García-Martínez, R. and Zepeda-Acosta, B. (2014) Activity Induced by a Naphthalene-Prazosin Derivative on Ischemia/Reperfusion Injury in Rats. Pharmacology & Pharmacy, 5, 1130-1142. doi: 10.4236/pp.2014.512123.


[1] Lim, G. (2012) Acute Coronary Syndromes: Reduced Mortality from MI in Denmark, England, and Poland. National Reviews of Cardiology, 9, 186.
[2] Thygesen, K., Alpert, J. and White, H. (2007) Universal Definition of Myocardial Infarction. Journal of American College of Cardiology, 60, 2173-2195.
[3] Pfeffe, M. (1995) Left Ventricular Remodeling after Acute Myocardial Infarction. Annual Review of Medicine, 46, 455-466.
[4] Klone, R., Przyklener, K. and Whittaker, P. (1989) Deterious Effects of Oxygen Radicals in Ischemia/Reperfusion. Circulation, 80, 1115-1127.
[5] Kusumoto, K., Haist, J. and Karmazyn, M. (2001) Na(+)/H(+) Exchange Inhibition Reduces Hypertrophy and Heart Failure after Myocardial Infarction in Rats. American Journal Physiology, Heart Circulatory Physiology, 280, H738-H745.
[6] Gross, E., Hsu, A. and Gross, G. (2004) Opioid-Induced Cardioprotection Occurs via Glycogen Synthase Kinase Beta Inhibition during Reperfusion in Intact Rat Hearts. Circulation Research, 94, 960-966.
[7] Hanlon, P., Fu, P., Wright, G., et al. (2005) Mechanisms of Erythropoietin-Mediated Cardioprotection during Ischemia-Reperfusion Injury: Role of Protein Kinase C and Phosphatidylinositol 3-Kinase Signaling. The Journal of Federation of American Societies for Experimental Biology, 19, 1323-1325.
[8] Cole, W., McPherson, C. and Sontag, D. (1991) ATP-Regulated K+ Channels Protect the Myocardium against Ischemia/Reperfusion Damage. Circulation Research, 69, 571-581.
[9] Griffiths, E. and Halestrap, A. (1993) Protection by Cyclosporin A of Ischemia/Reperfusion-Induced Damage in Isolated Rat Hearts. Journal of Molecular and Cellular Cardiology, 25, 1461-1469.
[10] Rossoni, R., Manfredi, B. and Cavalca, V., et al. (2003) The Aminotetraline Derivative (±)-(R,S)-5,6-Dihydroxy-2-Methylamino-1,2,3,4-Tetrahydro-Naphthalene Hydrochloride (CHF-1024) Displays Cardioprotection in Postischemic Ventricular Dysfunction of the Rat Heart. Journal of Pharmacology and Experimental Therapeutics, 307, 633-639.
[11] Sugawara, E., Nakayama, Y., Senoo, Y., et al. (1991) Protective Effects of Calmodulin Antagonists (Trifluoperazine and W-7) on Hypothermic Ischemic Rat Hearts. Acta Medica Okayama, 45, 129-134.
[12] Yang, T.-L., Chen, M.-F., Jiang, J.-L., Xie, Q.-Y., Li, Y.-P. and Li, Y.-J. (2005) The Endothelin Receptor Antagonist Decreases Ischemia/Reperfusion-Induced Tumor Necrosis Factor Production in Isolated Rat Hearts. International Journal of Cardiology, 100, 495-498.
[13] Kristek, F. and Koprdova, R. (1977) Long-Term Effect of Prazosin Administration on Blood Pressure Heart and Structure of Coronary Artery of Young Spontaneously Hypertensive Rats. Journal of Physiology and Pharmacology, 62, 295-301.
[14] Bengtsson, C., Johnsson, G. and Regardh, C.G. (1975) Plasma Levels and Effects of Metoprolol on Blood Pressure and Heart Rate in Hypertensive Patients after an Acute Dose and between Two Doses during Long-Term Treatment. Clinical Pharmacology and Therapeutics, 17, 400-408.
[15] Blouin, M., Han, Y., Burch, J., Farand, J., Mellon, C., Gaudreault, M., et al. (2010) The Discovery of 4-{1-[({2,5-Dimethyl-4-[4-(trifluoromethyl)benzyl]-3-thienyl}carbonyl)amino]cyclopropyl}benzoic Acid (MK-2894), A Potent and Selective Prostaglandin E2 Subtype 4 Receptor Antagonist. Journal of Medicinal Chemistry, 53, 2227-2238.
[16] Henry, P. (1980) Comparative Pharmacology of Calcium Antagonists: Nifedipine, Verapamil and Diltiazem. The American Journal of cardiology, 46, 1047-1058.
[17] Bayne, K. (1996) Revised Guide for the Care and Use of Laboratory Animals Available. The Physiologist, 9, 208-211.
[18] Figueroa-Valverde, L., Díaz-Cedillo, F., López-Ramos, M., García-Cervera, E. and Quijano-Ascencio, K. (2011) Inotropic Activity Induced by Carbamazepine-AlKyne Derivative in an Isolated Heart Model and Perfused to Constant Flow. Biomedica, 31, 232-241.
[19] Booth, E., Obeid, N. and Lucchesi, B. (2005) Activation of Estrogen Receptor-α Protects the in Vivo Rabbit Heart from Ischemia-Reperfusion Injury. American Journal of Physiology, Heart and Circulatory Physiology, 289, H2039-H2047.
[20] Figueroa-Valverde, L., Díaz-Cedillo, F., Díaz-Ku, E. and Camacho-Luis, A. (2009) Effect Induced by Hemisuccinate of Pregnenolone on Perfusion Pressure and Vascular Resistance Rat Heart. African Journal of Pharmacy and Pharmacology, 3, 234-241.
[21] Szokodi, I., Kinnunen, P., Tavi, P., Weckstrom, M., Toth, M. and Ruskoaho, H. (1998) Evidence for cAMP-Independent Mechanisms Mediating the Effects of Adrenomedullin, a New Inotropic Peptide. Circulation, 97, 1062-1070.
[22] Hocht, C., Opezzo, J., Gorzalczany, S., et al. (1999) Una Aproximación Cinética y Dinámica de Metildopa en Ratas con Coartación Aórtica Mediante Microdiálisis. Revista Argentina de Cardiologia, 67, 769-773.
[23] Weber, G. and Farris, F. (1979) Synthesis and Spectral Properties of a Hydrophobic Fluorescent Probe: 6-Propionyl-2-(dimethylamino)naphthalene. Biochemistry, 18, 3075-3078.
[24] House, H., Koepsell, D. and Campbell, W. (1972) Synthesis of Some Diphenyl and Triphenyl Derivatives of Anthracene and Naphthalene. Journal of Organic Chemistry, 37, 1003-1011.
[25] Yoshikawa, E. and Yoshinori, Y. (2000) Palladium-Catalyzed Intermolecular Controlled Insertion of Benzyne-Benzyne-Alkene and Benzyne-Alkyne-Alkene-Synthesis of Phenanthrene and Naphthalene Derivatives. Angewandte Chemie International Edition, 39, 173-175.<173::AID-ANIE173>3.0.CO;2-F
[26] Node, K., Kitakaze, M., Kosaka, H., Minamino, T., Funaya, H. and Hori, M. (1977) Amelioration of Ischemia- and Reperfusion-Induced Myocardial Injury by 17β-Estradiol: Role of Nitric Oxide and Calcium-Activated Potassium Channels. Circulation, 96, 1953-1963.
[27] Suparto, I., Koudy, W. and Fox, J. (2005) A Comparison of Two Progestins on Myocardial Ischemia-Reperfusion Injury in Ovariectomized Monkeys Receiving Estrogen Therapy. Coronary Artery Disease, 16, 301-308.
[28] Jeanes, H.L., Wanikiat, P., Sharif, I. and Gray, G.A. (2006) Medroxyprogesterone Acetate Inhibits the Cardioprotective Effect of Estrogen in Experimental Ischemia-Reperfusion Injury. Menopause, 13, 80-86.
[29] Bouïs, D., Hospers, G. and Meijer, C. (2001) Endothelium in Vitro: A Review of Human Vascular Endothelial Cell Lines for Blood Vessel-Related Research. Angiogenesis, 4, 91-102.
[30] Beer, S., Reincke, M. and Kral, M. (2002) Susceptibility to Cardiac Ischemia/Reperfusion Injury Is Modulated by Chronic Estrogen Status. Journal of Cardiovascular Pharmacology, 40, 420-428.
[31] Seillan, C., Ody, C., Russo-Marie, F. and Duval, D. (1983) Differential Aspects of Sex Steroids on Prostaglandin Secretion by Male and Female Cultured Piglet Endothelial Cells. Prostaglandins, 26, 3-12.
[32] Figueroa-Valverde, L., Díaz-Cedillo, F. and López-Ramos, M. (2011) Design and Synthesis of an Estradiol Derivative and Evaluation of Its Inotropic Activity in Isolated Rat Heart. African Journal of Pharmacy and Pharmacology, 5, 1703-1712.
[33] Toit, E., Muller, C. and McCarthy, J. and Opie, L.H. (1999) Levosimendan: Effects of a Calcium Sensitizer on Function and Arrhythmias and Cyclic Nucleotide Levels during Ischemia/Reperfusion in the Langendorff-Perfused Guinea Pig Heart. Journal of Pharmacology and Experimental Therapeutics, 290, 505-514.
[34] Ririe, D., Butterworth, J., Royster, R., McGregor, D. and Zaloga, G.P. (1995) Triiodothyronine Increases Contractility Independent of β-Adrenergic Receptors or Stimulation of Cyclic-3’,5’-Adenosine Monophosphate. Anesthesiology, 82, 1004-1012.

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