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The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes

Item Type:Article
Title:The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes
Creators Name:Savoia, C. and Arrabito, E. and Parente, R. and Sada, L. and Madaro, L. and Nicoletti, C. and Zezza, L. and Alonzo, A. and Rubattu, S. and Michelini, S. and Muller, D.N. and Volpe, M.
Abstract:We tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodeling of resistance arteries in double transgenic rats (dTGR). dTGR (5 weeks) were treated with aliskiren (3 mg/kg/day) or ramipril (1 mg/kg/day) for 14 days and compared with age-matched vehicle-treated dTGR. Blood pressure was similarly reduced in both aliskiren-treated and ramipril-treated rats compared to control dTGR (167±1 mmHg and 169±2 mmHg vs 197+/-4vmmHg, respectively P<0.05). Media-to-lumen ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared to controls (6.3+/-0.5 % and 6.4+/-0.2 % vs 9.8+/-0.4%, respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren treated rats. eNOS expression showed a 2-fold increase only in aliskiren-treated dTGR as compared to controls (P<0.01) and ramipril-treated dTGR (p<0.05). Plasma nitrite, as an index of NO production, was significantly increased in dTGR treated with either aliskiren or ramipril compared to controls. Only aliskiren induced a 2-fold increase of plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91phox expression and reactive oxygen species production in aorta were significantly and similarly reduced by both drugs. In conclusion equieffective hypotensive doses of aliskiren or ramipril reduced M/L of mesenteric arteries and improved oxidative stress in dTGR. However, only aliskiren increased further NO production in the vasculature. Hence, in dTGR direct renin inhibition induces favorable effects similar to that induced by ACE inhibition in improving vascular remodeling through different mechanisms.
Keywords:Nitric Oxide, Renin Inhibition, Reactive Oxygen Species (ROS), Small Artery, Vascular Remodelling, Animals, Rats
Source:Clinical Science
Publisher:Portland Press
Page Range:183-189
Date:1 August 2013
Official Publication:https://doi.org/10.1042/CS20120395
PubMed:View item in PubMed

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