51. Combined Aliskiren and L-arginine treatment reverses renovascular hypertension in an animal model
- Author
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Cíntia Helena Santuzzi, Sonia Alves Gouvea, Erick Rg Claudio, Gláucia R. Abreu, Vinicius Mengal, Renata Tiradentes, Nazaré Souza Bissoli, Henrique de Azevedo Futuro Neto, and N.F. Silva
- Subjects
Male ,medicine.medical_specialty ,Sympathetic Nervous System ,Physiology ,Urinary system ,Renal function ,Blood Pressure ,Arginine ,Kidney ,Renovascular hypertension ,chemistry.chemical_compound ,Chlorides ,Fumarates ,Internal medicine ,Internal Medicine ,medicine ,Animals ,Urea ,Rats, Wistar ,Endothelial dysfunction ,Antihypertensive Agents ,business.industry ,Sodium ,Water ,Aliskiren ,medicine.disease ,Amides ,Angiotensin II ,Rats ,Hypertension, Renovascular ,medicine.anatomical_structure ,Endocrinology ,Blood pressure ,chemistry ,Nitric Oxide Synthase ,Cardiology and Cardiovascular Medicine ,business ,Glomerular Filtration Rate - Abstract
Renovascular hypertension is characterized by increased renal sympathetic activity, angiotensin II and by endothelial dysfunction. The purpose of this study was to determine the role of renal sympathetic nerve activity (RSNA) in mediating the anti-hypertensive effects of aliskiren (ALSK) and L-arginine (L-ARG) in a rat renovascular hypertension model. Hypertension was induced by clipping the right renal artery, and the following five groups were divided: SHAM operated; 2-kidney, 1-clip (2K1C); 2K1C plus ALSK; 2K1C plus L-ARG; and 2K1C plus ALSK+ L-ARG. The systolic blood pressure (SBP) of 2K1C rats increased from 114.4±5.2 to 204±12.7 mm Hg (P0.05) and was only reduced by ALSK+L-ARG treatment (138.4±4.37 mm Hg). The 2K1C hypertension increased the baseline RSNA (SHAM: 62.4±6.39 vs. 2K1C: 97.4±8.43%). L-ARG or ALSK+L-ARG treatment significantly decreased baseline RSNA (2K1C L-ARG:70.7±2.39; 2K1C ALSK+L-ARG: 69.3±4.23%), but ALSK treatment alone did not (2K1C ALSK: 84.2±2.5%). Urinary water, Na(+), Cl(-) and urea excretion were similar in the 2K1C L-ARG, 2K1C ALSK+L-ARG and SHAM groups. The combination of ALSK+L-ARG restored urine flow and increased the glomerular filtration rate. The nNOS expression in the non clipped kidney was significantly increased in 2K1C ALSK+L-ARG rats. In conclusion, combined ALSK+L-ARG treatment normalizes SBP and prevents renal dysfunction in 2K1C hypertensive rats.
- Published
- 2015