Combined Aliskiren and L-arginine treatment reverses renovascular hypertension in an animal model.
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 (P<0.05) 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.
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Renata V
RV
Tiradentes
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Cintia H
CH
Santuzzi
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Erick Rg
ER
Claudio
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Vinicius
V
Mengal
Department of Morphology, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Nyam F
NF
Silva
1] Department of Morphology, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil [2] Univix Medical School, Vitória-ES, Brazil [3] Emescam Medical School, Vitória-ES, Brazil.
Henrique A F
HA
Neto
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Nazaré S
NS
Bissoli
Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil.
Glaucia R
GR
Abreu
1] Department of Physiological Sciences, Health Sciences Center, Federal University of Espírito Santo, Vitória-ES, Brazil [2] Nucleus of Biotechnology, Centro de Ciências da Saúde, Federal University of Espirito Santo (UFES), Vitória-ES, Brazil.
Sonia A
SA
Gouvea
D000577:Amides / Q000627:therapeutic use*; D000818:Animals; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D001120:Arginine / Q000627:therapeutic use*; D001794:Blood Pressure; D002712:Chlorides / Q000652:urine; D005650:Fumarates / Q000627:therapeutic use*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000473:pathology; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000652:urine; D013564:Sympathetic Nervous System / Q000187:drug effects; D014508:Urea / Q000652:urine; D014867:Water / Q000378:metabolism
D000577:Amides; D000959:Antihypertensive Agents; D002712:Chlorides; D005650:Fumarates; D014867:Water; C446481:aliskiren; D014508:Urea; D001120:Arginine; D012964:Sodium; D019001:Nitric Oxide Synthase