Beneficial Changes Promoted by L‐arginine and Aliskiren in Resistance Vessels in 2K1C hypertensive rats

Abstract

Renovascular hypertension is characterized by increased angiotensin II and oxidative stress and by endothelial dysfunction. By acting on multiple targets and promoting diverse actions, angiotensin II (Ang II) plays a pivotal role in vascular dysfunction. The purpose of this study was to test whether the administration of aliskiren (ALSK) and L‐arginine (L‐arg) would restore endothelial dysfunction and reduce inflammation and oxidative stress 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 vascular reactivity to norepinephrine (NE; 10(−9) to 2 × 10(−3) mol/L) and acetylcholine (ACh; 10(−10) to 10(−3) mol/L) was evaluated in the mesenteric arteriolar bed through concentration‐effect curves. The structure was assessed by histology and biomolecular analyzes were done via western blot, lipid peroxidation, DHE and DAF. For 4 weeks, blood pressure (BP) was monitored and endothelium‐dependent vasoconstriction and relaxation were assessed in mesenteric arteriolar. ALSK+L‐arg reduced BP and the contractile response to norepinephrine and improved acetylcholine relaxation. Incubation with N‐nitro‐L‐arginine methyl ester (L‐NAME) and L‐NAME+ Indometacin increased the response to norepinephrine in the 2K1C group and the effect was greater and partially improved, respectively, with the treatments. However, It was improved acetylcholine relaxation with the both of the treatments. The bioavailability of nitric oxide increased with the treatments, and the inflammation and oxidative stress was reduced with the treatments. L‐arginine and aliskiren attenuates the morphofunctional deleterious effects of Ang II on resistance vessels. The benefits of L‐arginine and aliskiren seem to occur through restoring the balance of ROS/NO. Therefore, this study opened new avenues for further clinical targeting of the treatment of cardiovascular diseases related to activation of the renin‐angiotensin system. In conclusion, combined ALSK+L‐arg treatment normalizes BP and prevents endothelial dysfunction in 2K1C hypertensive rats.Support or Funding InformationThis research was supported by a CNPq research grants. This study was funded by Fundação de Amparo a Pesquisa do Espirito Santo (FAPES‐Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq‐Brazil).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.