In the present study, we tested the hypothesis that chronic treatment with the direct rennin inhibitor aliskiren improves the remodelling of resistance arteries in dTGR (double-transgenic rats). dTGR (5 weeks) were treated with aliskiren (3 mg/kg of body mass per day) or ramipril (1 mg/kg of body mass per day) for 14 days and compared with age-matched vehicle-treated dTGR. BP (blood pressure) was similarly reduced in both aliskiren-treated and ramipril-treated rats compared with control dTGR (167±1 and 169±2 mmHg compared with 197±4 mmHg respectively; P<0.05). The M/L (media-to-lumen) ratio assessed on pressurized preparations was equally reduced in aliskiren-treated and ramipril-treated rats compared with controls (6.3±0.5 and 6.4±0.2% compared with 9.8±0.4% respectively; P<0.05). Endothelium-dependent and -independent relaxations were similar among the groups. L-NAME (NG-nitro-L-arginine methyl ester) significantly reduced acetylcholine-induced dilation in drug-treated dTGR. This effect was significantly more prominent in aliskiren-treated rats. eNOS (endothelial NO synthase) expression showed a 2-fold increase only in aliskiren-treated dTGR as compared with 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 with controls. Only aliskiren induced a 2-fold increase in plasma nitrite, which was significantly greater than that induced by ramipril (P<0.05). gp91phox expression and ROS (reactive oxygen species) production in aorta were significantly and similarly reduced by both drugs. In conclusion, equieffective hypotensive doses of aliskiren or ramipril reduced the M/L ratio 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 favourable effects similar to that induced by ACE (angiotensin-converting enzyme) inhibition in improving vascular remodelling through different mechanisms.
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Research Article|
May 01 2013
The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes
Carmine Savoia;
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
Correspondence: Professor Carmine Savoia (email [email protected]).
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Emanuele Arrabito;
Emanuele Arrabito
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Rosa Parente;
Rosa Parente
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Lidia Sada;
Lidia Sada
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Luca Madaro;
Luca Madaro
†DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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Carmine Nicoletti;
Carmine Nicoletti
†DAHFMO-Unit of Histology and Medical Embryology, Sapienza University of Rome, Rome, Italy
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Luigi Zezza;
Luigi Zezza
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Alessandro Alonzo;
Alessandro Alonzo
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Speranza Rubattu;
Speranza Rubattu
‡IRCCS Neuromed, Pozzilli, IS, Italy
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Serena Michelini;
Serena Michelini
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
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Dominik N. Muller;
Dominik N. Muller
§Max-Delbruck Center for Molecular Medicine, Berlin, Germany
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Massimo Volpe
Massimo Volpe
*Division of Cardiology, Department of Clinical and Molecular Medicine, Sant'Andrea Hospital, Sapienza University of Rome, Rome, Italy
‡IRCCS Neuromed, Pozzilli, IS, Italy
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Publisher: Portland Press Ltd
Received:
July 30 2012
Revision Received:
February 22 2013
Accepted:
February 26 2013
Accepted Manuscript online:
February 26 2013
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© The Authors Journal compilation © 2013 Biochemical Society
2013
Clin Sci (Lond) (2013) 125 (4): 183–189.
Article history
Received:
July 30 2012
Revision Received:
February 22 2013
Accepted:
February 26 2013
Accepted Manuscript online:
February 26 2013
Citation
Carmine Savoia, Emanuele Arrabito, Rosa Parente, Lidia Sada, Luca Madaro, Carmine Nicoletti, Luigi Zezza, Alessandro Alonzo, Speranza Rubattu, Serena Michelini, Dominik N. Muller, Massimo Volpe; The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes. Clin Sci (Lond) 1 August 2013; 125 (4): 183–189. doi: https://doi.org/10.1042/CS20120395
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