The aim of this study was to determinate the gene expression levels of angiotensinogen, angiotensin converting enzyme, renin, (pro)renin receptor, and the final rennin-angiotensin system (RAS) products Angiotensin (Ang) II and Ang 1-7 inthe remnant kidney of 5/6 nephrectomized rats and its response to RAS pharmacological blockade. Male Wistar rats were divided into five groups: sham operated (SO), 5/6 nephrectomized (NFX), NFX + captopril (50 mg/ kg/day), NFX + losartan (10 mg/kg/day), and NFX + aliskiren (10 mg/kg/day). Animals were followed up for 60 days and protein urine excretion was measured. Systolic blood pressure, renal tissue RAS mRNA expression levels, plasma Ang II, and plasma Ang 1-7 were evaluated at day 60 after nephrectomy. Blood pressure and urine protein were increased after 5/6 nephrectomy. Ang II levels were increased 9.4 fold, whereas Ang 1-7 decreased 72.9% in NFX animals compared with SO rats. 5/6 nephrectomy increased renal angiotensinogen and (pro)renin receptor mRNA expression but down-regulated renin mRNA expression. RAS blockade restored the systolic blood pressure to normal values and slowed down urinary protein excretion, and also prevented changes in Ang II and Ang 1-7. RAS blockade reduced (pro)renin receptor, ACE, and AGT mRNA expression in the remnant kidney. However, renin mRNA expression increased compared with NFX rats. In conclusion these results suggest that inhibition of Ang II synthesis by RAS blockade is associated with renal regulation of RAS mRNA expression and this may be through a mechanism related with the Ang II/Ang 1-7 balance.
Liang, P., Jones, C.A., Bisgrove, B.W., et al. (2004) Genomic characterization and expression analysis of the first non mammalian renin genes from zebrafish and pufferfish. Physiological Genomics, 16, 314-322. doi:10.1152/physiolgenomics.00012.2003
Kobori, H., Nangaku, M., Navar, L.G. and Nishiyama, A. (2007) The intrarenal renin angiotensin system: From physiology to the pathobiology of hypertension and kidney disease. Pharmacological Reviews, 59, 251-287. doi:10.1124/pr.59.3.3
Carey, R.M. and Siragy, H.M. (2003) Newly recognized components of the renin-angiotensin system: Potential roles in cardiovascular and renal regulation. Endocrine Reviews, 24, 261-271. doi:10.1210/er.2003-0001
Ribeiro-Oliveira Jr, A., Nogueira, A.I., Pereira, R.M., Boas, W.W., Dos Santos, R.A. and Simões e Silva, A.C. (2008) The renin-angiotensin system and diabetes: An update. Journal of Vascular Health and Risk Management, 4, 787-803.
Santos, R.A., Ferreira, A.J. and Simões e Silva, A.C. (2008) Recent advances in the angiotensin-converting enzyme 2-angiotensin (1-7)-Mas axis. Experimental Physiology, 93, 519-527. doi:10.1113/expphysiol.2008.042002
Schefe, J.H., Menk, M., Reinemund, J., Effertz, K., Hobbs, R.M., Pandolfi, P.P., Ruiz, P., Unger, T. and Funke-Kaiser, H. (2006) A novel signal transduction cascade involving direct physical interaction of the renin/ prorenin receptor with the transcription factor promyelocytic zinc finger protein. Circulation Research, 99, 1355-1366. doi:10.1161/01.RES.0000251700.00994.0d
Brasier, A.R., Jamaluddin, M., Han, Y., Patterson, C. and Runge, M.S. (2000) Angiotensin II induces gene transcription through cell-type-dependent effects on the nuclear factor-kappaB (NF-kappaB) transcription factor. Molecular and Cellular Biochemistry, 212, 155-169. doi:10.1023/A:1007133710837
Kang, J.J., Toma, I., Sipos, A., Meer, E.J., Vargas, S.L. and Peti-Peterdi, J. (2008) The collecting duct is the major source of prorenin in diabetes. Hypertension, 51, 1597-1604. doi:10.1161/HYPERTENSIONAHA.107.107268
Prieto-Carrasquero, M.C., Kobori, H., Ozawa, Y., Gutierrez, A., Seth, D. and Navar, L.G. (2005) AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Renal Physiology: American Journal of Physiology, 289, F632-F637.
Prieto-Carrasquero, M.C., Botros, F.T., Pagan, J., et al. (2008) Collecting duct renin is upregulated in both kidneys of 2-kidney, 1-clip goldblatt hypertensive rats. Hypertension, 51, 1590-1596. doi:10.1161/HYPERTENSIONAHA.108.110916
Krskova, K., Filipcik, P., Zilka, N., et al. (2011) Angiotensinogen and angiotensin-converting enzyme mRNA decrease and AT1 receptor mRNA and protein increase in epididymal fat tissue accompany age-induced elevation of adiposity and reductions in expression of GLUT4 and peroxisome proliferator-activated receptor (PPARγ). Journal of Physiology and Pharmacology, 62, 403-410.
Arellano-Mendoza, M.G., Vargas-Robles, H., Del Valle- Mondragon, L., Rios, A. and Escalante, B. (2011) Prevention of renal injury and endothelial dysfunction by chronic L-arginine and antioxidant treatment. Renal Failure, 33, 47-53. doi:10.3109/0886022X.2010.541583
Bradford, M.M. (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye-binding. Analytical Biochemistry, 72, 248-254. doi:10.1016/0003-2697(76)90527-3
Cervantes-Pérez, L.G., Ibarra-Lara, M.L., Rubio, M.E., et al. (2010) Effect of clofibrate on vascular reactivity in a model of high blood pressure secondary to aortic coarctation. Pharmacological Reports, 62, 874-882.
Tenorio-López, F.A., Zarco-Olvera, G., Sánchez-Mendoza, A., Rosas-Peralta, M., Pastelín-Hernández, G. and del Valle-Mondragón, L. (2010) Simultaneous determination of angiotensins II and 1-7 by capillary zone electrophoresis in plasma and urine from hypertensive rats. Talanta, 80, 1702-1712. doi:10.1016/j.talanta.2009.10.010
Livak, K.J. and Schmittgen, T.D. (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25, 402-408. doi:10.1006/meth.2001.1262
Sanchez, P.L., Salgado, L.M., Ferreri, N.R. and Escalante, B. (1999) Effect of cyclooxygenase-2 inhibition on renal function after renal ablation. Hypertension, 34, 848-853. doi:10.1161/01.HYP.34.4.848
Rakusan, D., Kujal, P., Kramer, H.J., et al. (2010) Persistent antihypertensive effect of Aliskiren is accompanied by reduced proteinuria and normalization of glomerular area in Ren-2 transgenic rats. American Journal of Physiology-Renal Physiology, 299, F758-F766. doi:10.1152/ajprenal.00259.2010
Gross, O., Girgert, R., Rubel, D., Temme, J., Theissen, S. and Müller, G.A. (2011) Renal protective effects of Aliskiren beyond its antihypertensive property in a mouse model of progressive fibrosis. American Journal of Hypertension, 24, 355-361. doi:10.1038/ajh.2010.231
Velkoska, E., Dean, R.G., Burchill, L., Levidiotis, V. and Burrell, L.M. (2010) Reduction in renal ACE2 expression in subtotal nephrectomy in rats is ameliorated with ACE inhibition. Clinical Science (Lond)., 118, 269-279. doi:10.1042/CS20090318
Iyer, S.N., Yamada, K., Diz, D.I., Ferrario, C.M. and Chappell, M.C. (2000) Evidence that prostaglandins mediate the antihypertensive actions of angiotensin-(1-7) during chronic blockade of the renin-angiotensin system. Journal of Cardiovascular Pharmacology, 36, 109-117. doi:10.1097/00005344-200007000-00015
Nakamura, S., Averill, D.B., Chappell, M.C., Diz, D.I., Brosnihan, K.B. and Ferrario, C.M. (2003) Angiotensin receptors contribute to blood pressure homeostasis in salt-depleted SHR. American Journal of Physiology— Regulatory, Integrative and Comparative Physiology, 284, R164-R173.
Rusai, K., Schmaderer, C., Hermans, J.J., Lutz, J., Heemann, U. and Baumann, M. (2011) Direct renin inhibition in a rat model of chronic allograft injury. Transplantation, 92, 999-1004.
Hirose, T., Mori, N., Totsune, K., Morimoto, R., Maejima, T., Kawamura, T., Metoki, H., Asayama, K., Kikuya, M., Ohkubo, T., Kohzuki, M., Takahashi, K. and Imai, Y. (2010) Increased expression of (pro)renin receptor in the remnant kidneys of 5/6 nephrectomized rats. Regulatory Peptides, 8, 93-99. doi:10.1016/j.regpep.2009.11.006
da Silveira, K.D., Pompermayer Bosco, K.S., et al. (2010) ACE2-angiotensin-(1-7)-Mas axis in renal ischaemia/reperfusion injury in rats. Clinical Science (Lond), 119, 385-394. doi:10.1042/CS20090554
Dilauro, M., Zimpelmann, J., Robertson, S.J., Genest, D. and Burns, K.D. (2010) Effect of ACE2 and angiotensin(1-7) in a mouse model of early chronic kidney disease. American Journal of Physiology—Renal Physiology, 298, F1523-F1532. doi:10.1152/ajprenal.00426.2009
Tallant, E.A., Ferrario, C.M. and Gallagher, P.E. (2005) Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. American Journal of Physiology Heart and Circulatory Physiology, 289, H1560-H1566. doi:10.1152/ajpheart.00941.2004
Pinheiro, S.V. and Simões e Silva, A.C. (2012) Angiotensin converting enzyme 2, Angiotensin-(1-7), and receptor MAS axis in the kidney. International Journal of Hypertension, 2012, 414128. doi:10.1155/2012/414128