Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats

Abstract

The aim of this study\rwas to determinate the gene expression levels of angiotensinogen, angiotensin\rconverting enzyme, renin, (pro)renin receptor, and the final rennin-angiotensin\rsystem (RAS) products Angiotensin (Ang) II and Ang 1-7 inthe remnant kidney of 5/6\rnephrectomized rats and its response to RAS pharmacological blockade. Male\rWistar rats were divided into five groups: sham operated (SO), 5/6\rnephrectomized (NFX), NFX + captopril (50 mg/ kg/day), NFX + losartan (10\rmg/kg/day), and NFX + aliskiren (10 mg/kg/day). Animals were followed up for\r60 days and protein urine excretion was measured. Systolic blood pressure,\rrenal tissue RAS mRNA expression levels, plasma Ang II, and plasma Ang 1-7 were\revaluated at day 60 after nephrectomy. Blood pressure and urine protein were\rincreased after 5/6 nephrectomy. Ang II levels were increased 9.4 fold,\rwhereas Ang 1-7 decreased 72.9% in NFX animals compared with SO rats. 5/6 nephrectomy\rincreased renal angiotensinogen and (pro)renin receptor mRNA expression but\rdown-regulated renin mRNA expression. RAS blockade restored the systolic blood\rpressure to normal values and slowed down urinary protein excretion, and also\rprevented changes in Ang II and Ang 1-7. RAS blockade reduced (pro)renin\rreceptor, ACE, and AGT mRNA expression in the remnant kidney. However, renin\rmRNA expression increased compared with NFX rats. In conclusion these results\rsuggest that inhibition of Ang II synthesis by RAS blockade is associated\rwith renal regulation of RAS mRNA expression and this may be through a mechanism\rrelated with the Ang II/Ang 1-7 balance.