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

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

Research output: Contribution to journalArticle

Abstract

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; Pphox 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.

Original languageEnglish
Pages (from-to)183-189
Number of pages7
JournalClinical Science
Volume125
Issue number4
DOIs
Publication statusPublished - Aug 2013

Keywords

  • Nitric oxide
  • Reactive oxygen species (ROS)
  • Renin inhibition
  • Small artery
  • Vascular remodelling

ASJC Scopus subject areas

  • Medicine(all)

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  • Cite this

    Savoia, C., Arrabito, E., Parente, R., Sada, L., Madaro, L., Nicoletti, C., Zezza, L., Alonzo, A., Rubattu, S., Michelini, S., Muller, D. N., & Volpe, M. (2013). The direct renin inhibitor aliskiren improves vascular remodelling in transgenic rats harbouring human renin and angiotensinogen genes. Clinical Science, 125(4), 183-189. https://doi.org/10.1042/CS20120395