Submitted by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2014-12-17T13:10:33Z No. of bitstreams: 2 dirceu_de_souza_melo.pdf: 1243588 bytes, checksum: e609b2371fe339ca91cc379149b3beca (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2014-12-17T13:13:48Z (GMT) No. of bitstreams: 2 dirceu_de_souza_melo.pdf: 1243588 bytes, checksum: e609b2371fe339ca91cc379149b3beca (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2014-12-17T13:13:44Z (GMT) No. of bitstreams: 2 dirceu_de_souza_melo.pdf: 1243588 bytes, checksum: e609b2371fe339ca91cc379149b3beca (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Approved for entry into archive by Rodrigo Martins Cruz (rodrigo.cruz@ufvjm.edu.br) on 2014-12-17T13:14:26Z (GMT) No. of bitstreams: 2 dirceu_de_souza_melo.pdf: 1243588 bytes, checksum: e609b2371fe339ca91cc379149b3beca (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) / Made available in DSpace on 2014-12-17T13:14:27Z (GMT). No. of bitstreams: 2 dirceu_de_souza_melo.pdf: 1243588 bytes, checksum: e609b2371fe339ca91cc379149b3beca (MD5) license_rdf: 22974 bytes, checksum: 99c771d9f0b9c46790009b9874d49253 (MD5) Previous issue date: 2013 / Evid?ncias recentes sugerem que a restri??o cal?rica intensa (RCI) (>40%) exerce efeitos ben?ficos sobre o cora??o de ratos. No entanto, a maioria destes estudos avaliaram os efeitos da RCI em cora??es de ratos que iniciaram esta restri??o j? na idade adulta. Neste trabalho, investigamos as conseq??ncias de uma restri??o cal?rica de 50% desde o nascimento sobre a fun??o e morfologia card?aca de ratos adultos e avaliamos os poss?veis mecanismos envolvidos nestas adapta??es. Desde o nascimento at? a idade de 90 dias ratos RC50 tiveram sua alimenta??o restrita a 50% do consumo do grupo ad libitum (AL). Durante o per?odo de 90 dias os animais tiveram sua ingest?o alimentar, peso corporal e press?o arterial monitorados. Ap?s este per?odo, foi realizado um teste de capacidade aer?bica m?xima para avaliar indiretamente a fun??o cardiovascular global. Quarenta e oito horas ap?s este teste os animais foram eutanasiados, o sangue foi coletado para an?lise do hemat?crito, bioqu?mica s?rica e estresse oxidativo e o m?sculo s?leo retirado para an?lise do estresse oxidativo. A t?bia foi retirada para aferi??o do comprimento e f?gado, ba?o, supra-renais, test?culos e gordura viceral removidos para aferi??o do peso. O cora??o foi retirado e o ?ndice de desenvolvimento de tens?o m?xima (+dT/dt) e m?nima (-dT/dt) do mioc?rdio foram analisados pela prepara??o de cora??o isolado. Tamb?m foi realizada an?lise do estresse oxidativo card?aco e o di?metro, n?mero e densidade de cardiomi?citos, assim como os n?veis de fibrose card?aca foram obtidos atrav?s da an?lise histol?gica. Mi?citos ventriculares foram isolados para avalia??o do transiente de Ca2+ em microscopia confocal e os n?veis de fosforila??o da Akt e express?o da SERCA2 foram avaliados pela t?cnica de Western blot. Comparado ao grupo AL, os animais RC50 apresentaram menor peso corporal e de ?rg?os, menor comprimento da t?bia, menor glicemia, maior colesterol HDL, menor press?o arterial, menor estresse oxidativo card?aco, maior desempenho aer?bio e da fun??o card?aca, como mostrado pelo aumento ?dT/dt. Apesar do menor di?metro dos cardiomi?citos, ratos RC50 apresentaram aumento na rela??o cora??o/peso corporal, aumento do n?mero e densidade dos cardiomi?citos, e n?veis semelhantes de fibrose card?aca em compara??o aos animais AL. Os n?veis de fosforila??o da Akt foram superiores nos cardiomi?citos dos animais RC50 e n?o houve diferen?as significativas no transiente de Ca2+ e na express?o de SERCA2 entre os cardiomi?citos dos animais RC50 e AL. Em conjunto, estas observa??es revelaram efeitos positivos de uma RCI de 50% desde o nascimento sobre a fun??o, estrutura card?aca e vias de sinaliza??o da sobreviv?ncia de cardiomi?citos em ratos adultos. / Disserta??o (Mestrado) ? Programa Multic?ntrico de P?s-gradua??o em Ci?ncias Fisiol?gicas, Universidade Federal dos Vales do Jequitinhonha e Mucuri, 2013. / ABSTRACT There has been growing evidence suggesting that a severe caloric restriction (SCR) (above 40%) leads to beneficial effects on heart rats. However, most of the reports are focused on the effects of SCR on hearts of rats which started this restriction at adulthood. In this work, we investigated the consequences of a 50% caloric restriction since birth on cardiac morphology and function in adult rats and evaluated the possible mechanisms involved in these adaptations. From birth up to the age of 90 days CR50 rats were fed restricted at 50% of the Ad Libitum group (AL). During the period of 90 days the animals had their food intake, body weight and blood pressure monitored. After this period, a maximal aerobic test was performed in order to indirectly evaluate the global cardiovascular function. Forty-eight hours after this test the animals were euthanized the blood collected for analysis of hematocrit, serum biochemistry and oxidative stress and soleus muscle collected for oxidative stress analysis. The tibia was removed for measurement of length and liver, spleen, adrenals, testes and visceral fat were removed for measurement of weight. The heart was removed and the index of velocity of myocardial contraction (+dT/dt) and relaxation (-dT/dt) was analyzed by isolated heart preparation. We also carried out analysis of cardiac oxidative stress and cardiomyocyte diameter, number, density and myocardium collagen content were obtained through histological analysis. Ventricular myocytes were isolated by standard methods in order to evaluate phosphorylated AKT levels and the expression of SERCA2a was assessed by Western blot. Compared to AL, CR50 animals had lower body and organs weight, lower tibia length, lower blood glucose, higher HDL cholesterol, lower blood pressure, lower oxidative stress in the heart and blood, increased aerobic performance and cardiac function, as shown by increased ? dT/dt. Despite the smaller cardiomyocyte diameter, CR50 rats presented increased heart/body weight ratio, increased cardiomyocyte density and number, and similar levels of myocardium collagen content compared to AL rats. AKT was hyperphosphorylated in cardiomyocytes from CR50 rats and no significant differences in Ca2+ transient and SERCA2 levels were found between cardiomyocytes of CR50 and AL rats. Collectively, these observations revealed beneficial effects of a 50% caloric restriction from birth on cadiac function, structure and signaling pathways for survival of adult rat cardimyocytes.