Submitted by Celso Magalhaes (celsomagalhaes@ufrrj.br) on 2018-03-26T14:34:13Z
No. of bitstreams: 1
2015 - Fernando de Azevedo da Cruz Seara.pdf: 1716878 bytes, checksum: 6a6ea74b23b441a8aafb15e937dea036 (MD5) / Made available in DSpace on 2018-03-26T14:34:14Z (GMT). No. of bitstreams: 1
2015 - Fernando de Azevedo da Cruz Seara.pdf: 1716878 bytes, checksum: 6a6ea74b23b441a8aafb15e937dea036 (MD5)
Previous issue date: 2015-07-24 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / According to World Health Organization, ischemia heart diseases are the leading cause of death worldwide. Among therapeutic approaches, reperfusion is the most effective and indicated is reperfusion. Despite the better post-infarction prognostic, absolute improvement on cardiac function is hardly achieved due to ischemia/reperfusion injury (IRI). Within this context, anabolic steroids (AS) administration, in adult Wistar rats, significantly increase IRI susceptibility. Moreover, chronic administration of AS, during adolescent phase, induces persistent cardiovascular dysfunctions along adulthood. Therefore, the aim of the present study was to analyze the effects of chronic administration of supraphysiologic doses of testosterone propionate, during adolescent phase, in the susceptibility to ischemia/reperfusion injury, in adult Wistar rats. To perform it, 24 Wistar rats were allocated into two groups, AS (Testosterone propionate 5 mg kg-1, since 26? day postnatal, 5 days per week, during 5 weeks) and Control (Vehicle). In the 82? postnatal, rats were euthanized and hearts, livers, lungs, kidneys and testicles were collected. Isolated hearts were artificially perfused with modified Krebs-Henseleit solution, through Langendorff apparatus, and, then, submitted to ex vivo ischemia ? reperfusion protocol (20 minutes of stabilization, 30 minutes of global ischemia and 60 minutes of reperfusion). The left ventricle (LV) end diastolic- LVEDP), systolic- (LVSP) and developed pressures (LVDP), as well as first derivatives of pressure, maximum and minimum (dP/dt, maximum and minimum, respectively) were measured through an intraventricular latex balloon, connected to a pressure transducer. Through the electrocardiogram, susceptibility to arrhythmic episodes was analyzed. At the end of the protocol, area of infarct was delimited and gene expression of ? and ? myosin heavy chains and Glyceraldehyde 3-phosphate dehydrogenase, as well as the activity of nicotinamide adenine dinucleotide phosphate-oxidase (Nox) enzymes, were calculated. In comparison to Control group, hearts from AS group presented: Hypertrophy, due to an increase in cardiac mass (33%, P<0,001) and index (37%, P<0,001); Significantly increase in the area of infarct (54,76%, P<0,05); Worst recovery of both LVEDP and LVDP, along reperfusion; Less recovery of maximum dP/dt, during reperfusion, despite the equivalent LVSP; Reduced basal minimum dP/dt and, subsequently, reduction in the recovery of the aforementioned parameter, regarding reperfusion period; Enhanced gene expression of MHC? (%), consistent with the loss of mechanical performance; Increased incidence of arrhythmic episodes in the reperfusion period (100%, P<0,01). No statistical difference could be seen in regard to the Nox activity. For the first time, we demonstrated that AS treatment during adolescent phase promotes cardiac hypertrophy and gene reprogramming, both persistent during adulthood, besides an increase susceptibility to IRI, through in the larger area of infarct and poor recovery of cardiac electrical and mechanical proprieties, in isolated hearts of adult Wistar rats / De acordo com a OMS, as doen?as isqu?micas do cora??o consistem na maior causa mortis global. Dentre as abordagens terap?uticas, a mais eficaz ? a reperfus?o. A despeito da melhora no progn?stico p?s-infarto, a recupera??o plena da fun??o card?aca dificilmente ? alcan?ada, devido a inj?ria de isquemia/reperfus?o (IIR). Neste contexto, a administra??o de EA em ratos Wistar adultos enaltece a susceptibilidade ? IIR. Ademais, a administra??o de EA em ratos Wistar, ao longo da adolesc?ncia, favorece o desenvolvimento de disfun??es cardiovasculares persistentes durante a fase adulta. Desta forma, objetivou-se, com o presente estudo, analisar os efeitos da sobrecarga cr?nica de propionato de testosterona, ao longo da fase adolescente, na susceptibilidade ? IIR, em ratos Wistar adultos. Para tanto, foram utilizados 24 ratos Wistar machos, divididos em dois grupos: EA (Propionato de testosterona 5 mg kg-1, a partir do 26? dia p?s-natal, 5 vezes por semana/ 5 semanas) e CTL (ve?culo). No 82? dia p?s-natal, os ratos foram submetidos ? eutan?sia para a coleta ?rg?os. Os cora??es isolados foram submetidos ? perfus?o artificial em aparato de Langendorff, e, assim, ao protocolo de isquemia/reperfus?o. As press?es diast?lica final (PDF), sist?lica (PS) e desenvolvida (PD), do ventr?culo esquerdo (VE), e as primeiras derivadas de press?o do VE, m?xima e m?nima (dP/dt m?xima e m?nima, respectivamente), foram mensuradas atrav?s de um bal?o de l?tex intraventricular, conectado a um transdutor de press?o. Atrav?s do eletrocardiograma, foi analisada a susceptibilidade aos epis?dios arr?tmicos. Ao final do protocolo, as ?reas de infarto foram demarcadas e a express?o g?nica das cadeias pesadas de miosina e gliceralde?do-3-fosfato desidrogenase, assim como a atividade enzimas da fam?lia de niconinam?da adenina dinucleot?deo fosfato oxidase (Nox), no ventr?culo esquerdo, foram avaliadas. Em rela??o ao grupo Controle, os cora??es dos animais tratados com EA apresentaram: Hipertrofia, atrav?s do aumento na massa (aumento de 33%, P<0,001) e do ?ndice card?aco (aumento de 37%, P<0,001); aumento significativo da ?rea de infarto (aumento de 54,76%, P<0,05); T?nue recupera??o da PDFVE, assim como da PDVE, durante a reperfus?o; Inferior recupera??o da dP/dt m?xima, ao longo da reperfus?o, a despeito da equivalente recupera??o na PSVE; Reduzida dP/dt m?nima basal e, subsequentemente, redu??o na recupera??o deste par?metro, ao longo da reperfus?o; Aumento significativo da express?o g?nica da MHC? (P<0,01), condizente o preju?zo no desempenho mec?nico; Maior incid?ncia de epis?dios arr?tmicos, ao longo da reperfus?o (aumento de 100%, P<0,01). N?o houve diferen?a em rela??o ?s atividades das Nox. Pela primeira vez, foi demonstrado que a administra??o de EA, ao longo da adolesc?ncia, provoca hipertrofia e reprograma??o g?nica card?aca, persistente durante a fase adulta, al?m de aumentar, significativamente, a susceptibilidade ? IIR, por meio do aumento na ?rea de infarto e piora na recupera??o das propriedades mec?nicas e el?tricas card?acas, em cora??es isolados de ratos Wistar adultos.
| Identifer | oai:union.ndltd.org:IBICT/oai:localhost:jspui/2236 |
| Date | 24 July 2015 |
| Creators | Seara, Fernando de Azevedo Cruz |
| Contributors | Olivares, Emerson Lopes, Almeida, Norma Aparecida dos Santos, Carvalho, Adriana Bastos de |
| Publisher | Universidade Federal Rural do Rio de Janeiro, Programa de P?s-Gradua??o em Ci?ncias Fisiol?gicas, UFRRJ, Brasil, Instituto de Ci?ncias Biol?gicas |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Biblioteca Digital de Teses e Dissertações da UFRRJ, instname:Universidade Federal Rural do Rio de Janeiro, instacron:UFRRJ |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 1 (SIH/SUS), S. D. I. H. D. S. Valor servi?os hospitalares segundo Regi?o. SA?DE, M. D. Cap?tulo CID-10: IX. Doen?as do aparelho circulat?rio: Per?odo: Dez/2014 p. 2014. 2 AHLGRIM, C.; GUGLIN, M. Anabolics and cardiomyopathy in a bodybuilder: case report and literature review. J Card Fail, v. 15, n. 6, p. 496-500, Aug 2009. 3 ALMAAS, V. M. et al. Increased amount of interstitial fibrosis predicts ventricular arrhythmias, and is associated with reduced myocardial septal function in patients with obstructive hypertrophic cardiomyopathy. Europace, v. 15, n. 9, p. 1319-27, Sep 2013. 4 ALTSCHULD, R. A.; HOSTETLER, J. R.; BRIERLEY, G. P. Response of isolated rat heart cells to hypoxia, re-oxygenation, and acidosis. Circ Res, v. 49, n. 2, p. 307-16, Aug 1981. 5 ALVES, M. J. et al. Abnormal neurovascular control in anabolic androgenic steroids users. Med Sci Sports Exerc, v. 42, n. 5, p. 865-71, May 2010. 6 AMEZIANE-EL-HASSANI, R. et al. Dual oxidase-2 has an intrinsic Ca2+-dependent H2O2-generating activity. J Biol Chem, v. 280, n. 34, p. 30046-54, Aug 2005. 7 AON, M. A. et al. Synchronized whole cell oscillations in mitochondrial metabolism triggered by a local release of reactive oxygen species in cardiac myocytes. J Biol Chem, v. 278, n. 45, p. 44735-44, Nov 2003. 8 APPELL, H. J. et al. Ultrastructural and morphometric investigations on the effects of training and administration of anabolic steroids on the myocardium of guinea pigs. Int J Sports Med, v. 4, n. 4, p. 268-74, Nov 1983. 9 AZHAR, S.; MENON, K. Receptor-mediated gonadotropin action in the ovary. Rat luteal cells preferentially utilize and are acutely dependent upon the plasma lipoprotein-supplied sterols in gonadotropin-stimulated steroid production. Journal of Biological Chemistry, v. 256, n. 13, p. 6548-6555, 1981. 10 BAE, S.; ZHANG, L. Gender differences in cardioprotection against ischemia/reperfusion injury in adult rat hearts: focus on Akt and protein kinase C signaling. J Pharmacol Exp Ther, v. 315, n. 3, p. 1125-35, Dec 2005. 75 11 BARRON, H. V. et al. Use of reperfusion therapy for acute myocardial infarction in the United States Data from the National Registry of Myocardial Infarction 2. Circulation, v. 97, n. 12, p. 1150-1156, 1998. 12 BARTH, W. et al. Differential remodeling of the left and right heart after norepinephrine treatment in rats: studies on cytokines and collagen. J Mol Cell Cardiol, v. 32, n. 2, p. 273-84, Feb 2000. 13 BEKKERING, S. et al. Oxidized low-density lipoprotein induces long-term proinflammatory cytokine production and foam cell formation via epigenetic reprogramming of monocytes. Arteriosclerosis, thrombosis, and vascular biology, v. 34, n. 8, p. 1731-1738, 2014. 14 BELL, J. R. et al. Aromatase deficiency confers paradoxical postischemic cardioprotection. Endocrinology, v. 152, n. 12, p. 4937-47, Dec 2011. 15 BERNAUER, W.; ERNENPUTSCH, I. Antagonistic effects of alpha-adrenoceptor blocking agents on arrhythmias, enzyme release, and myocardial necrosis in isolated rat hearts with coronary occlusion and reperfusion. Naunyn Schmiedebergs Arch Pharmacol, v. 338, n. 1, p. 88-95, Jul 1988. 16 BEUTEL, A.; BERGAMASCHI, C. T.; CAMPOS, R. R. Effects of chronic anabolic steroid treatment on tonic and reflex cardiovascular control in male rats. J Steroid Biochem Mol Biol, v. 93, n. 1, p. 43-8, Jan 2005. 17 BISHOP, S.; WHITE, F.; BLOOR, C. Regional myocardial blood flow during acute myocardial infarction in the conscious dog. Circulation research, v. 38, n. 5, p. 429-438, 1976. 18 BORUTAITE, V. et al. Inhibition of mitochondrial permeability transition prevents mitochondrial dysfunction, cytochrome c release and apoptosis induced by heart ischemia. J Mol Cell Cardiol, v. 35, n. 4, p. 357-66, Apr 2003. 19 BRADFORD, M. A rapid and sensitive technique to determine protein concentrations. Anal. Biochem, v. 72, p. 248-254, 1976. 20 BRAUNWALD, E.; KLONER, R. The stunned myocardium: prolonged, postischemic ventricular dysfunction. Circulation, v. 66, n. 6, p. 1146-1149, 1982. 21 BRILLA, C. G.; JANICKI, J. S.; WEBER, K. T. Impaired diastolic function and coronary reserve in genetic hypertension. Role of interstitial fibrosis and medial thickening of intramyocardial coronary arteries. Circ Res, v. 69, n. 1, p. 107-15, Jul 1991. 76 22 BROWN-S?QUARD, C. E. On a New Therapeutic Method Consisting in the Use of Organic Liquids Extracted from Glands and Other Organs. Br Med J, v. 1, n. 1692, p. 1145-7, Jun 1893. 23 BROWN, D. A. et al. Susceptibility of the heart to ischaemia-reperfusion injury and exercise-induced cardioprotection are sex-dependent in the rat. J Physiol, v. 564, n. Pt 2, p. 619-30, Apr 2005. 24 CALOVINI, T.; HAASE, H.; MORANO, I. Steroid-hormone regulation of myosin subunit expression in smooth and cardiac muscle. J Cell Biochem, v. 59, n. 1, p. 69-78, Sep 1995. 25 CARLINI, E. et al. I Levantamento domiciliar sobre o uso de drogas psicotr?picas no Brasil: estudo envolvendo as 107 maiores cidades do pa?s. S?o Paulo: Cebrid/Unifesp, 2002. 26 CARLINI, E. V Levantamento Nacional sobre o consumo de drogas psicotr?picas entre estudantes do ensino fundamental e m?dio da rede p?blica de ensino nas 27 capitais brasileiras: 2004. In: (Ed.). V Levantamento Nacional sobre o Consumo de Drogas Psicotr?picas entre Estudantes do Ensino Fundamental e M?dio da Rede P?blica de Ensino nas 27 Capitais Brasileiras: 2004: UNIFESP Centro Brasileiro de informa??es sobre Drogas Psicotr?picas, 2005. 27 ______. IV Levantamento Nacional sobre o Consumo de Drogas Psicotr?picas entre Estudantes do Ensino Fundamental e M?dio da Rede P?blica de Ensino nas 27 Capitais Brasileiras - 2010. In: (Ed.). IV Levantamento Nacional sobre o Consumo de Drogas Psicotr?picas entre Estudantes do Ensino Fundamental e M?dio da Rede P?blica de Ensino nas 27 Capitais Brasileiras - 2010: UNIFESP Centro Brasileiro de informa??es sobre Drogas Psicotr?picas, 2011. 28 CARLINI, E. A. II levantamento domiciliar sobre o uso de drogas psicotr?picas no Brasil: estudo envolvendo as 108 maiores cidades do pa?s: 2005. Senad, 2007. 29 CASAGRANDE, V. et al. Overexpression of tissue inhibitor of metalloproteinase 3 in macrophages reduces atherosclerosis in low-density lipoprotein receptor knockout mice. Arteriosclerosis, thrombosis, and vascular biology, v. 32, n. 1, p. 74-81, 2012. 30 CAVE, A. C. et al. ATP synthesis during low-flow ischemia influence of increased glycolytic substrate. Circulation, v. 101, n. 17, p. 2090-2096, 2000. 31 CHAN, M. Y. et al. Long-term mortality of patients undergoing cardiac catheterization for ST-elevation and non-ST-elevation myocardial infarction. Circulation, v. 119, n. 24, p. 3110-3117, 2009. 77 32 CHAVES, E. A. et al. Nandrolone decanoate impairs exercise-induced cardioprotection: role of antioxidant enzymes. J Steroid Biochem Mol Biol, v. 99, n. 4-5, p. 223-30, Jun 2006. 33 CHEN, X. et al. Ca2+ Influx?Induced Sarcoplasmic Reticulum Ca2+ Overload Causes Mitochondrial-Dependent Apoptosis in Ventricular Myocytes. Circulation research, v. 97, n. 10, p. 1009-1017, 2005. 34 CHEN, Y. F.; NAFTILAN, A. J.; OPARIL, S. Androgen-dependent angiotensinogen and renin messenger RNA expression in hypertensive rats. Hypertension, v. 19, n. 5, p. 456-63, May 1992. 35 CHIGNALIA, A. Z. et al. Testosterone induces vascular smooth muscle cell migration by NADPH oxidase and c-Src?dependent pathways. Hypertension, v. 59, n. 6, p. 1263-1271, 2012. 36 COHEN, M. V.; YANG, X.-M.; DOWNEY, J. M. The pH hypothesis of postconditioning staccato reperfusion reintroduces oxygen and perpetuates myocardial acidosis. Circulation, v. 115, n. 14, p. 1895-1903, 2007. 37 COOPER, R. et al. Trends and disparities in coronary heart disease, stroke, and other cardiovascular diseases in the United States findings of the national conference on cardiovascular disease prevention. Circulation, v. 102, n. 25, p. 3137-3147, 2000. 38 COSEMANS, J. M. et al. Key role of glycoprotein Ib/V/IX and von Willebrand factor in platelet activation-dependent fibrin formation at low shear flow. Blood, v. 117, n. 2, p. 651-660, 2011. 39 COSTARELLA, C. E. et al. Testosterone causes direct relaxation of rat thoracic aorta. J Pharmacol Exp Ther, v. 277, n. 1, p. 34-9, Apr 1996. 40 CYBULSKY, M. I.; GIMBRONE, M. Endothelial expression of a mononuclear leukocyte adhesion molecule during atherogenesis. Science, v. 251, n. 4995, p. 788-791, 1991. 41 DAI, D. F. et al. Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res, v. 108, n. 7, p. 837-46, Apr 2011. 42 DAVIDSON, S. M. et al. Slow calcium waves and redox changes precede mPTP opening in the intact heart during hypoxia and reoxygenation. Cardiovascular research, p. cvr349, 2011. 43 DEMYANETS, S. et al. Interleukin-33 induces expression of adhesion molecules and inflammatory activation in human endothelial cells and in human atherosclerotic plaques. Arteriosclerosis, thrombosis, and vascular biology, v. 31, n. 9, p. 2080-2089, 2011. 78 44 DETEN, A. et al. Cardiac cytokine expression is upregulated in the acute phase after myocardial infarction. Experimental studies in rats. Cardiovascular research, v. 55, n. 2, p. 329-340, 2002. 45 DING, A. Q.; STALLONE, J. N. Testosterone-induced relaxation of rat aorta is androgen structure specific and involves K+ channel activation. Journal of Applied Physiology, v. 91, n. 6, p. 2742-2750, 2001. 46 DOROSHOW, J. H.; DAVIES, K. J. Redox cycling of anthracyclines by cardiac mitochondria. II. Formation of superoxide anion, hydrogen peroxide, and hydroxyl radical. J Biol Chem, v. 261, n. 7, p. 3068-74, Mar 1986. 47 DOTSON, J. L.; BROWN, R. T. The history of the development of anabolic-androgenic steroids. Pediatr Clin North Am, v. 54, n. 4, p. 761-9, xi, Aug 2007a. 48 ______. The history of the development of anabolic-androgenic steroids. Pediatric Clinics of North America, v. 54, n. 4, p. 761-769, 2007b. 49 DUDNAKOVA, T. V. et al. Alterations in myocardial ultrastructure and protein expression after a single injection of isoproterenol. Molecular and cellular biochemistry, v. 252, n. 1-2, p. 173-181, 2003. 50 DURANT, R. H. et al. Use of multiple drugs among adolescents who use anabolic steroids. N Engl J Med, v. 328, n. 13, p. 922-6, Apr 1993. 51 EITZMAN, D. T. et al. Plasminogen activator inhibitor-1 deficiency protects against atherosclerosis progression in the mouse carotid artery. Blood, v. 96, n. 13, p. 4212-4215, 2000. 52 ENDEMANN, D. H. et al. Eplerenone prevents salt-induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats. Hypertension, v. 43, n. 6, p. 1252-7, Jun 2004. 53 ENDOH, A. et al. The zona reticularis is the site of biosynthesis of dehydroepiandrosterone and dehydroepiandrosterone sulfate in the adult human adrenal cortex resulting from its low expression of 3 beta-hydroxysteroid dehydrogenase. The Journal of Clinical Endocrinology & Metabolism, v. 81, n. 10, p. 3558-3565, 1996. 54 ER, F. et al. Impact of testosterone on cardiac L-type calcium channels and Ca2+ sparks: acute actions antagonize chronic effects. Cell Calcium, v. 41, n. 5, p. 467-77, May 2007. 55 FANTON, L. et al. Heart lesions associated with anabolic steroid abuse: comparison of post-mortem findings in athletes and norethandrolone-induced lesions in rabbits. Exp Toxicol Pathol, v. 61, n. 4, p. 317-23, Jul 2009. 79 56 FERRARI, M.; MCANELLY, M.; ZAKON, H. Individual variation in and androgen-modulation of the sodium current in electric organ. The Journal of neuroscience, v. 15, n. 5, p. 4023-4032, 1995. 57 FERREIRA, A. J.; SANTOS, R. A.; ALMEIDA, A. P. Angiotensin-(1-7): cardioprotective effect in myocardial ischemia/reperfusion. Hypertension, v. 38, n. 3 Pt 2, p. 665-8, Sep 2001. 58 FERRER, M. et al. Chronic treatment with the anabolic steroid, nandrolone, inhibits vasodilator responses in rabbit aorta. Eur J Pharmacol, v. 252, n. 2, p. 233-41, Feb 1994. 59 FINESCHI, V. et al. Anabolic steroid- and exercise-induced cardio-depressant cytokines and myocardial ?1 receptor expression in CD1 mice. Curr Pharm Biotechnol, v. 12, n. 2, p. 275-84, Feb 2011. 60 FORTEZA, R. et al. Regulated hydrogen peroxide production by Duox in human airway epithelial cells. Am J Respir Cell Mol Biol, v. 32, n. 5, p. 462-9, May 2005. 61 FRANCIS, J. et al. Progression of heart failure after myocardial infarction in the rat. American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, v. 281, n. 5, p. R1734-R1745, 2001. 62 FRANQUNI, J. V. et al. Nandrolone decanoate determines cardiac remodelling and injury by an imbalance in cardiac inflammatory cytokines and ACE activity, blunting of the Bezold-Jarisch reflex, resulting in the development of hypertension. Steroids, v. 78, n. 3, p. 379-85, Mar 2013. 63 FRENCH, J. P. et al. Ischemia-reperfusion-induced calpain activation and SERCA2a degradation are attenuated by exercise training and calpain inhibition. American Journal of Physiology-Heart and Circulatory Physiology, v. 290, n. 1, p. H128-H136, 2006. 64 FRIEHS, I.; DEL NIDO, P. J. Increased susceptibility of hypertrophied hearts to ischemic injury. Ann Thorac Surg, v. 75, n. 2, p. S678-84, Feb 2003. 65 FULLER, W. et al. Cardiac ischemia causes inhibition of the Na/K ATPase by a labile cytosolic compound whose production is linked to oxidant stress. Cardiovasc Res, v. 57, n. 4, p. 1044-51, Mar 2003. 66 GINKS, W. et al. Coronary artery reperfusion: II. Reduction of myocardial infarct size at 1 week after the coronary occlusion. Journal of Clinical Investigation, v. 51, n. 10, p. 2717, 1972. 67 GO, A. S. et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation, v. 127, n. 1, p. e6-e245, Jan 2013. 80 68 ______. An effective approach to high blood pressure control: a science advisory from the American Heart Association, the American College of Cardiology, and the Centers for Disease Control and Prevention. Journal of the American College of Cardiology, v. 63, n. 12, p. 1230-1238, 2014. 69 GOLDEN, K. L. et al. Gonadectomy alters myosin heavy chain composition in isolated cardiac myocytes. Endocrine, v. 24, n. 2, p. 137-40, Jul 2004. 70 GONZALES, R. J.; KRAUSE, D. N.; DUCKLES, S. P. Testosterone suppresses endothelium-dependent dilation of rat middle cerebral arteries. Am J Physiol Heart Circ Physiol, v. 286, n. 2, p. H552-60, Feb 2004. 71 GONZALES, R. J. et al. Testosterone treatment increases thromboxane function in rat cerebral arteries. Am J Physiol Heart Circ Physiol, v. 289, n. 2, p. H578-85, Aug 2005. 72 GORCZYNSKA, E.; HANDELSMAN, D. J. Androgens rapidly increase the cytosolic calcium concentration in Sertoli cells. Endocrinology, v. 136, n. 5, p. 2052-2059, 1995. 73 GRINO, P. B. et al. Androgen Resistance Associated With a Qualitative Abnormality of the Androgen Receptor and Responsive to High Dose Androgen Therapy*. The Journal of Clinical Endocrinology & Metabolism, v. 68, n. 3, p. 578-584, 1989. 74 GROH?, C. et al. Cardiac myocytes and fibroblasts contain functional estrogen receptors. FEBS Lett, v. 416, n. 1, p. 107-12, Oct 1997. 75 GUO, C. et al. A soluble receptor for advanced glycation end-products inhibits hypoxia/reoxygenation-induced apoptosis in rat cardiomyocytes via the mitochondrial pathway. International journal of molecular sciences, v. 13, n. 9, p. 11923-11940, 2012. 76 GUO, Z. et al. Nongenomic testosterone calcium signaling Genotropic actions in androgen receptor-free macrophages. Journal of Biological Chemistry, v. 277, n. 33, p. 29600-29607, 2002. 77 GUSTAFSON, T. A. et al. Hormonal regulation of myosin heavy chain and alpha-actin gene expression in cultured fetal rat heart myocytes. J Biol Chem, v. 262, n. 27, p. 13316-22, Sep 1987. 78 GUTH, B. D. et al. Regional myocardial blood flow, function and metabolism using phosphorus-31 nuclear magnetic resonance spectroscopy during ischemia and reperfusion in dogs. Journal of the American College of Cardiology, v. 10, n. 3, p. 673-681, 1987. 81 79 GUZIK, T. J. et al. Coronary artery superoxide production and nox isoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol, v. 26, n. 2, p. 333-9, Feb 2006. 80 HALL, J. et al. Selective inhibition of L-type Ca2+ channels in A7r5 cells by physiological levels of testosterone. Endocrinology, v. 147, n. 6, p. 2675-80, Jun 2006. 81 HAN, T. S.; BOULOUX, P. M. What is the optimal therapy for young males with hypogonadotropic hypogonadism? Clin Endocrinol (Oxf), v. 72, n. 6, p. 731-7, Jun 2010. 82 HARADA, M. et al. G-CSF prevents cardiac remodeling after myocardial infarction by activating the Jak-Stat pathway in cardiomyocytes. Nat Med, v. 11, n. 3, p. 305-11, Mar 2005. 83 HASSAN, A. F.; KAMAL, M. M. Effect of exercise training and anabolic androgenic steroids on hemodynamics, glycogen content, angiogenesis and apoptosis of cardiac muscle in adult male rats. Int J Health Sci (Qassim), v. 7, n. 1, p. 47-60, Jan 2013. 84 HAYASHIDANI, S. et al. Anti-monocyte chemoattractant protein-1 gene therapy attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation, v. 108, n. 17, p. 2134-2140, 2003. 85 HERN?NDEZ, J. S. et al. Crosstalk between AMPK activation and angiotensin II-induced hypertrophy in cardiomyocytes: the role of mitochondria. J Cell Mol Med, v. 18, n. 4, p. 709-20, Apr 2014. 86 HEYNDRICKX, G. et al. Depression of regional blood flow and wall thickening after brief coronary occlusions. American Journal of Physiology-Heart and Circulatory Physiology, v. 234, n. 6, p. H653-H659, 1978. 87 HUANG, C. et al. Testosterone-down-regulated Akt pathway during cardiac ischemia/reperfusion: a mechanism involving BAD, Bcl-2 and FOXO3a. J Surg Res, v. 164, n. 1, p. e1-11, Nov 2010. 88 HUANG, W.-C. et al. Classical macrophage activation up-regulates several matrix metalloproteinases through mitogen activated protein kinases and nuclear factor-?B. 2012. 89 HUIE, M. J. An acute myocardial infarction occurring in an anabolic steroid user. Med Sci Sports Exerc, v. 26, n. 4, p. 408-13, Apr 1994. 90 IMAHASHI, K. et al. Transgenic expression of Bcl-2 modulates energy metabolism, prevents cytosolic acidification during ischemia, and reduces ischemia/reperfusion injury. Circ Res, v. 95, n. 7, p. 734-41, Oct 2004. 82 91 ______. Overexpression of the Na+/H+ exchanger and ischemia-reperfusion injury in the myocardium. Am J Physiol Heart Circ Physiol, v. 292, n. 5, p. H2237-47, May 2007. 92 IZUMO, S. et al. Myosin heavy chain messenger RNA and protein isoform transitions during cardiac hypertrophy. Interaction between hemodynamic and thyroid hormone-induced signals. J Clin Invest, v. 79, n. 3, p. 970-7, Mar 1987. 93 JENSTER, G. et al. Identification of two transcription activation units in the N-terminal domain of the human androgen receptor. Journal of Biological Chemistry, v. 270, n. 13, p. 7341-7346, 1995. 94 JIANG, L. et al. Calpain-1 regulation of matrix metalloproteinase 2 activity in vascular smooth muscle cells facilitates age-associated aortic wall calcification and fibrosis. Hypertension, v. 60, n. 5, p. 1192-1199, 2012. 95 JOHNSON, J. L. et al. Matrix metalloproteinase (MMP)-3 activates MMP-9 mediated vascular smooth muscle cell migration and neointima formation in mice. Arteriosclerosis, thrombosis, and vascular biology, v. 31, n. 9, p. e35-e44, 2011. 96 JOHNSTON, L. D. et al. Monitoring the Future: National Survey Results on Drug Use, 1975-2009. Volume I: Secondary School Students. NIH Publication No. 10-7584. National Institute on Drug Abuse (NIDA), 2010. 97 KANNEL, W. B. et al. Coronary heart disease and atrial fibrillation: the Framingham Study. Am Heart J, v. 106, n. 2, p. 389-96, Aug 1983. 98 KANNEL, W. B. Left ventricular hypertrophy as a risk factor: the Framingham experience. Journal of hypertension. Supplement: official journal of the International Society of Hypertension, v. 9, n. 2, p. S3-8; discussion S8-9, 1991. 99 KASIKCIOGLU, E. et al. Aortic elastic properties in athletes using anabolic-androgenic steroids. Int J Cardiol, v. 114, n. 1, p. 132-4, Jan 2007. 100 KENNEDY, M. C.; LAWRENCE, C. Anabolic steroid abuse and cardiac death. Med J Aust, v. 158, n. 5, p. 346-8, Mar 1993. 101 KETTLE, A. J.; CARR, A. C.; WINTERBOURN, C. C. Assays using horseradish peroxidase and phenolic substrates require superoxide dismutase for accurate determination of hydrogen peroxide production by neutrophils. Free Radic Biol Med, v. 17, n. 2, p. 161-4, Aug 1994. 102 KHALIL, P. N. et al. Calpain inhibition reduces infarct size and improves global hemodynamics and left ventricular contractility in a porcine 83 myocardial ischemia/reperfusion model. European journal of pharmacology, v. 528, n. 1, p. 124-131, 2005. 103 KHURI, S. F. et al. The significance of the late fall in myocardial PCO2 and its relationship to myocardial pH after regional coronary occlusion in the dog. Circulation research, v. 56, n. 4, p. 537-547, 1985. 104 KIRCHHOFF, M. et al. Incidence of myocardial infarction in the Danish MONICA population 1982-1991. Int J Epidemiol, v. 28, n. 2, p. 211-8, Apr 1999. 105 KLEIN, H. H. et al. Na(+)/H(+) exchange inhibitor cariporide attenuates cell injury predominantly during ischemia and not at onset of reperfusion in porcine hearts with low residual blood flow. Circulation, v. 102, n. 16, p. 1977-82, Oct 2000. 106 KRAUSE, S.; HESS, M. L. Characterization of cardiac sarcoplasmic reticulum dysfunction during short-term, normothermic, global ischemia. Circulation research, v. 55, n. 2, p. 176-184, 1984. 107 KUBLI-GARFIAS, C. Ab initio comparative study of the electronic structure of testosterone, epitestosterone and androstenedione. Journal of Molecular Structure: THEOCHEM, v. 422, n. 1, p. 167-177, 1998. 108 KUIJPERS, M. J. et al. Factor XII regulates the pathological process of thrombus formation on ruptured plaques. Arteriosclerosis, thrombosis, and vascular biology, v. 34, n. 8, p. 1674-1680, 2014. 109 KUIL, C. W.; BERREVOETS, C. A.; MULDER, E. Ligand-induced Conformational Alterations of the Androgen Receptor Analyzed by Limited Trypsinization STUDIES ON THE MECHANISM OF ANTIANDROGEN ACTION. Journal of Biological Chemistry, v. 270, n. 46, p. 27569-27576, 1995. 110 KUSUMOTO, K.; HAIST, J. V.; KARMAZYN, M. Na(+)/H(+) exchange inhibition reduces hypertrophy and heart failure after myocardial infarction in rats. Am J Physiol Heart Circ Physiol, v. 280, n. 2, p. H738-45, Feb 2001. 111 LAGRANHA, C. J. et al. Sex differences in the phosphorylation of mitochondrial proteins result in reduced production of reactive oxygen species and cardioprotection in females. Circ Res, v. 106, n. 11, p. 1681-91, Jun 2010. 112 LANE, H. A. et al. Impaired vasoreactivity in bodybuilders using androgenic anabolic steroids. Eur J Clin Invest, v. 36, n. 7, p. 483-8, Jul 2006. 84 113 LEVY, B. I.; DURIEZ, M.; SAMUEL, J. L. Coronary microvasculature alteration in hypertensive rats. Effect of treatment with a diuretic and an ACE inhibitor. Am J Hypertens, v. 14, n. 1, p. 7-13, Jan 2001. 114 LEVY, D. et al. Risk of ventricular arrhythmias in left ventricular hypertrophy: the Framingham Heart Study. Am J Cardiol, v. 60, n. 7, p. 560-5, Sep 1987. 115 LI, G. et al. Catalase-overexpressing transgenic mouse heart is resistant to ischemia-reperfusion injury. American Journal of Physiology-Heart and Circulatory Physiology, v. 273, n. 3, p. H1090-H1095, 1997. 116 LIAO, R.; PODESSER, B. K.; LIM, C. C. The continuing evolution of the Langendorff and ejecting murine heart: new advances in cardiac phenotyping. Am J Physiol Heart Circ Physiol, v. 303, n. 2, p. H156-67, Jul 2012. 117 LOOR, G. et al. Mitochondrial oxidant stress triggers cell death in simulated ischemia?reperfusion. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, v. 1813, n. 7, p. 1382-1394, 2011. 118 LOSCHEN, G. et al. Superoxide radicals as precursors of mitochondrial hydrogen peroxide. FEBS Lett, v. 42, n. 1, p. 68-72, May 1974. 119 LOWE, J. E.; JENNINGS, R. B.; REIMER, K. A. Cardiac rigor mortis in dogs. Journal of molecular and cellular cardiology, v. 11, n. 10, p. 1017-1031, 1979. 120 LUCHNER, A. et al. Evaluation of brain natriuretic peptide as marker of left ventricular dysfunction and hypertrophy in the population. Journal of hypertension, v. 18, n. 8, p. 1121-1128, 2000. 121 LUIJKX, T. et al. Anabolic androgenic steroid use is associated with ventricular dysfunction on cardiac MRI in strength trained athletes. Int J Cardiol, v. 167, n. 3, p. 664-8, Aug 2013. 122 LUNDBERG, A. M. et al. Toll-like receptor 3 and 4 signalling through the TRIF and TRAM adaptors in haematopoietic cells promotes atherosclerosis. Cardiovascular research, v. 99, n. 2, p. 364-373, 2013. 123 MA, X. L. et al. Inhibition of p38 mitogen-activated protein kinase decreases cardiomyocyte apoptosis and improves cardiac function after myocardial ischemia and reperfusion. Circulation, v. 99, n. 13, p. 1685-91, Apr 1999. 124 MACKAY, J. et al. The atlas of heart disease and stroke. World Health Organization, 2004. ISBN 9241562765. 85 125 MAIOR, A. S. et al. Abnormal cardiac repolarization in anabolic androgenic steroid users carrying out submaximal exercise testing. Clin Exp Pharmacol Physiol, v. 37, n. 12, p. 1129-33, Dec 2010. 126 MANGAT, R. et al. Arterial retention of remnant lipoproteins ex vivo is increased in insulin resistance because of increased arterial biglycan and production of cholesterol-rich atherogenic particles that can be improved by ezetimibe in the JCR: LA-cp rat. Journal of the American Heart Association, v. 1, n. 5, p. e003434, 2012. 127 MARAVELIAS, C. et al. Adverse effects of anabolic steroids in athletes. A constant threat. Toxicol Lett, v. 158, n. 3, p. 167-75, Sep 2005. 128 MARON, B. J. Sudden death in young athletes. N Engl J Med, v. 349, n. 11, p. 1064-75, Sep 2003. 129 MARQUES-NETO, S. R. et al. AT1 and aldosterone receptors blockade prevents the chronic effect of nandrolone on the exercise-induced cardioprotection in perfused rat heart subjected to ischemia and reperfusion. Cardiovasc Drugs Ther, v. 28, n. 2, p. 125-35, Apr 2014. 130 MARQUES NETO, S. R. et al. The blockade of angiotensin AT1 and aldosterone receptors protects rats from synthetic androgen-induced cardiac autonomic dysfunction. Acta Physiol (Oxf), v. 208, n. 2, p. 166-71, Jun 2013. 131 MARTINDALE, J. J.; METZGER, J. M. Uncoupling of increased cellular oxidative stress and myocardial ischemia reperfusion injury by directed sarcolemma stabilization. Journal of molecular and cellular cardiology, v. 67, p. 26-37, 2014. 132 MCGOVERN, P. G. et al. Recent trends in acute coronary heart disease?mortality, morbidity, medical care, and risk factors. New England Journal of Medicine, v. 334, n. 14, p. 884-890, 1996. 133 MEDEI, E. et al. Chronic treatment with anabolic steroids induces ventricular repolarization disturbances: cellular, ionic and molecular mechanism. J Mol Cell Cardiol, v. 49, n. 2, p. 165-75, Aug 2010. 134 MENDIS, S.; PUSKA, P.; NORRVING, B. Global atlas on cardiovascular disease prevention and control. World Health Organization, 2011. ISBN 9241564377. 135 MINTO, C. F. et al. Pharmacokinetics and pharmacodynamics of nandrolone esters in oil vehicle: effects of ester, injection site and injection volume. J Pharmacol Exp Ther, v. 281, n. 1, p. 93-102, Apr 1997. 136 MISAO, J. et al. Expression of bcl-2 protein, an inhibitor of apoptosis, and Bax, an accelerator of apoptosis, in ventricular myocytes of human 86 hearts with myocardial infarction. Circulation, v. 94, n. 7, p. 1506-1512, 1996. 137 MIYATA, S. et al. Myosin heavy chain isoform expression in the failing and nonfailing human heart. Circ Res, v. 86, n. 4, p. 386-90, Mar 2000. 138 MOENS, A. L. et al. High-dose folic acid pretreatment blunts cardiac dysfunction during ischemia coupled to maintenance of high-energy phosphates and reduces postreperfusion injury. Circulation, v. 117, n. 14, p. 1810-1819, 2008. 139 MONTA?O, L. M. et al. Relaxation of androgens on rat thoracic aorta: testosterone concentration dependent agonist/antagonist L-type Ca2+ channel activity, and 5beta-dihydrotestosterone restricted to L-type Ca2+ channel blockade. Endocrinology, v. 149, n. 5, p. 2517-26, May 2008. 140 MORALES, A. J. et al. Effects of replacement dose of dehydroepiandrosterone in men and women of advancing age. The Journal of Clinical Endocrinology & Metabolism, v. 78, n. 6, p. 1360-1367, 1994. 141 MORANO, I. et al. Regulation of myosin heavy chain expression in the hearts of hypertensive rats by testosterone. Circ Res, v. 66, n. 6, p. 1585-90, Jun 1990. 142 MOZAFFARIAN, D. et al. Heart disease and stroke statistics--2015 update: a report from the American Heart Association. Circulation, v. 131, n. 4, p. e29-322, Jan 2015. 143 MULLIGAN, K. et al. Effect of nandrolone decanoate therapy on weight and lean body mass in HIV-infected women with weight loss: a randomized, double-blind, placebo-controlled, multicenter trial. Arch Intern Med, v. 165, n. 5, p. 578-85, Mar 2005. 144 MULVANY, M. J.; HALPERN, W. Contractile properties of small arterial resistance vessels in spontaneously hypertensive and normotensive rats. Circulation research, v. 41, n. 1, p. 19-26, 1977. 145 MYERS, C. The role of iron in doxorubicin-induced cardiomyopathy. Semin Oncol, v. 25, n. 4 Suppl 10, p. 10-4, Aug 1998. 146 NAGABABU, E.; CHREST, F. J.; RIFKIND, J. M. Hydrogen-peroxide-induced heme degradation in red blood cells: the protective roles of catalase and glutathione peroxidase. Biochim Biophys Acta, v. 1620, n. 1-3, p. 211-7, Mar 2003. 147 NAKAGAMI, H.; TAKEMOTO, M.; LIAO, J. K. NADPH oxidase-derived superoxide anion mediates angiotensin II-induced cardiac hypertrophy. J Mol Cell Cardiol, v. 35, n. 7, p. 851-9, Jul 2003. 87 148 NARITA, M. et al. Bax interacts with the permeability transition pore to induce permeability transition and cytochrome c release in isolated mitochondria. Proc Natl Acad Sci U S A, v. 95, n. 25, p. 14681-6, Dec 1998. 149 NICOLAY, K.; DE KRUIJFF, B. Effects of adriamycin on respiratory chain activities in mitochondria from rat liver, rat heart and bovine heart. Evidence for a preferential inhibition of complex III and IV. Biochim Biophys Acta, v. 892, n. 3, p. 320-30, Jul 1987. 150 NILSSON, S. Androgenic anabolic steroid use among male adolescents in Falkenberg. Eur J Clin Pharmacol, v. 48, n. 1, p. 9-11, 1995. 151 NILSSON, S. et al. The prevalence of the use of androgenic anabolic steroids by adolescents in a county of Sweden. Eur J Public Health, v. 11, n. 2, p. 195-7, Jun 2001. 152 NORMINGTON, K.; RUSSELL, D. W. Tissue distribution and kinetic characteristics of rat steroid 5 alpha-reductase isozymes. Evidence for distinct physiological functions. J Biol Chem, v. 267, n. 27, p. 19548-54, Sep 1992. 153 O'GARA, P. T. et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology, v. 61, n. 4, p. e78-e140, 2013. 154 OIKARINEN, L. et al. QRS duration and QT interval predict mortality in hypertensive patients with left ventricular hypertrophy: the Losartan Intervention for Endpoint Reduction in Hypertension Study. Hypertension, v. 43, n. 5, p. 1029-34, May 2004. 155 OJEDA, N. B. et al. Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring. Am J Physiol Regul Integr Comp Physiol, v. 298, n. 5, p. R1421-7, May 2010. 156 OKOSHI, M. P. et al. Aldosterone directly stimulates cardiac myocyte hypertrophy. J Card Fail, v. 10, n. 6, p. 511-8, Dec 2004. 157 OLIVARES, E. L. et al. Thyroid function disturbance and type 3 iodothyronine deiodinase induction after myocardial infarction in rats a time course study. Endocrinology, v. 148, n. 10, p. 4786-92, Oct 2007. 158 ______. Administration of an anabolic steroid durin |
Page generated in 0.0065 seconds