TITLE:
Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats
AUTHORS:
Erika Yadira Cruz-Laguna, Ana Ma. Gámez-Méndez, Hilda Vargas-Robles, Amelia Ríos, Alfonso Méndez-Tenorio, Bruno Escalante
KEYWORDS:
Angiotensin II; Angiotensin 1-7; ACE; RAS Blockade
JOURNAL NAME:
Health,
Vol.5 No.4A,
April
18,
2013
ABSTRACT: 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.