Combined Aliskiren and L-arginine treatment reverses renovascular hypertension in an animal model

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 (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.

Factors Associated with Outcomes of Percutaneous Transluminal Renal Angioplasty in Patients with Renal Artery Stenosis: A Retrospective Analysis of 50 Consecutive Cases

“…Percutaneous transluminal renal angioplasty (PTRA) has been one of the common treatments for RAS despite recent developments in therapeutics [2, 3]. Using retrospective data, Bonelli et al reported that 60–90% of 320 RAS patients who underwent PTRA exhibited some benefits after PTRA [4].…”

Aliskiren improves endothelium‐dependent relaxation of thoracic aorta by activating PI3K/Akt/eNOS signal pathway in SHR

“…11 In contrast to conventional rennin-angiotensin system (RAS) blockers, aliskiren blocks the renin system by directly inhibiting plasma renin activity and prevents the formation of both angiotensin I (Ang I) and angiotensin II (Ang II). 12 Accumulating experimental and clinical evidence support that aliskiren has demonstrated antihypertensive efficacy comparable with or even superior to that of other classes of antihypertensive drugs, including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin AT1-receptor blockers (ARBs). 13,14 Evidence has suggested that aliskiren improves endotheliumdependent vasodilation and NO availability in the peripheral resistance arterioles of hypertensive patients.…”

“…Aliskiren, a novel non‐peptide and oral renin inhibitor, has been approved for the treatment of hypertension . In contrast to conventional rennin–angiotensin system (RAS) blockers, aliskiren blocks the renin system by directly inhibiting plasma renin activity and prevents the formation of both angiotensin I (Ang I) and angiotensin II (Ang II) . Accumulating experimental and clinical evidence support that aliskiren has demonstrated antihypertensive efficacy comparable with or even superior to that of other classes of antihypertensive drugs, including angiotensin converting enzyme inhibitors (ACEIs) and angiotensin AT1‐receptor blockers (ARBs) …”