Studies indicate that the renal sympathetic activity plays an important role in progression of renovascular hypertension and tissue damages. The aim of this study is to elucidate the effects of combination Aliskiren (ALK) and L-arginine (L-ARG) on the blood pressure and renal sympathetic activity. Renovascular hypertension (2K1C) was produced in Male Wistar rats (140-160 g). Seven days after the renal artery clipped was performed by plethysmography to measure systolic blood pressure (SBP). The rats were divided in groups:Sham (n=6), 2K1C (n=7), 2K1C treated with aliskiren 50 mg/kg (ALK, n=9), 2K1C treated with L-arg 300 mg/kg (L-ARG, n=9) and 2K1C treated with a combination of ALK and L-arg (ALK + L-ARG, n=10). The treatment was performed for 21 days by gavage. At the end of treatment was made new plethysmography and the urine collection of 24 hours. The animals were anesthetized with urethane (1.2 g/Kg) for direct measurement of SBP and recording of renal nerve activity (RNA). At the end of the protocol, blood samples were taken and analyzed the expression of endothelial nitric oxide synthase (eNOS) in both kidneys by Western blotting. Statistical analysis was determined using 1-way ANOVA and Tukey test. Values are expressed as mean ± SEM and the significance of P <0.05. Only the treatment with the combination of ALK + L-arg was able to normalize SBP (138 ± 4.4 mmHg) compared to groups 2K1C, ALK and L-ARG (204 ± 12.7; 202 ± 17.7 and 176 ± 9 mmHg), since values were similar to SHAM (114 ± 5.2 mmHg). Similarly, the basal RNA in ALK + L-ARG and L-ARG was also normalized (SHAM: 62 ± 6.4; 2K1C: 97 ± 8.4; ALK: 84 ± 2.5; L-ARG: 71 ± 3.1 and ALK + L-ARG: 64 ± 3.4%) and an improvement of sympathetic responsiveness to changes in SBP in ALK + L-ARG group (SHAM: -54 ± 6.1; 2K1C: -25 ± 3.2; ALK: -30 ± 3.8; L-ARG: -34 ± 3.6 and ALK + L-ARG: -55 ± 6.1% Δ ANR with phenylephrine and SHAM: 78 ± 15.6; 2K1C: 13 ± 2.8; ALK: 21 ± 3.67; L-ARG: 38 ± 3.4 and ALK + L-ARG: 49 ± 8.79% Δ ANR with NPS). The animals L-ARG and ALK + L-ARG had natriuretic effect (SHAM: 148 ± 14.13; 2K1C: 48 ± 7.93; ALK: 48 ± 9.25; L-ARG: 121 ± 8.1 and ALK + L-ARG: 129 ± 7.8 mEq/L) and a tendency to present diuretic effect (SHAM: 20 ± 2; 2K1C: 11 ± 0.5; ALK: 9 ± 0.7; L-ARG: 17 ± 2.3 and ALK + L-ARG: 16 ± 2.1 mL/day) and improve urinary flow (SHAM: 0.014 ± 0.001; 2K1C: 0.008 ± 0.001; ALK: 0.006 ± 0.001; L-ARG: 0.011 ± 0.001 and ALK + L-ARG: 0.011 ± 0.001 ml / min), besides improving glomerular filtration rate (ALK + L-ARG: 2.06 ± 0.49; L-ARG: 1.73 ± 0.38; 2K1C: 0.35 ± 0.1; ALK: 0.45 ± 0.1). There was an increased eNOS expression only in the kidney clipped. The combination of ALK and L-ARG was able to reduce the sympathetic hyperactivity, increased diuresis, natriuresis and improved glomerular filtration rate, that contribute to reduce the arterial pressure levels.
37th Congress of IUPS (Birmingham, UK) (2013) Proc 37th IUPS, PCC096
Poster Communications: Aliskiren and L-arginine reduce the renal sympathetic activity and improves renal function in rats with renovascular hypertension
V. Mengal1, R. Tiradentes1, H. Futuro Neto1, N. Silva1, P. Matos1, A. Carvalho1, S. Gouvea1, G. R. Abreu1
1. Physiological Sciences, Federal University of Espirito Santo, Vitoria, Espirito Santo, Brazil.
View other abstracts by:
Where applicable, experiments conform with Society ethical requirements.