Angiotensin-(1-7) exerts a protective action in a rat model of ventilator-induced diaphragmatic dysfunction.

Autor: Zambelli V; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Sigurtà A; Anesthesia and Critical Care, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Rizzi L; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Zucca L; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Delvecchio P; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Bresciani E; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Torsello A; Department of Medicine, University of Milano-Bicocca, Monza, Italy., Bellani G; Department of Medicine, University of Milano-Bicocca, Monza, Italy. giacomo.bellani1@unimib.it.
Jazyk: angličtina
Zdroj: Intensive care medicine experimental [Intensive Care Med Exp] 2019 Jan 18; Vol. 7 (1), pp. 8. Date of Electronic Publication: 2019 Jan 18.
DOI: 10.1186/s40635-018-0218-x
Abstrakt: Background: Ventilator-induced diaphragmatic dysfunction (VIDD) is a common event during mechanical ventilation (MV) leading to rapid muscular atrophy and contractile dysfunction. Recent data show that renin-angiotensin system is involved in diaphragmatic skeletal muscle atrophy after MV. In particular, angiotensin-II can induce marked diaphragm muscle wasting, whereas angiotensin-(1-7) (Ang-(1-7)) could counteract this activity. This study was designed to evaluate the effects of the treatment with Ang-(1-7) in a rat model of VIDD with neuromuscular blocking agent infusion. Moreover, we studied whether the administration of A-779, an antagonist of Ang-(1-7) receptor (Mas), alone or in combination with PD123319, an antagonist of AT2 receptor, could antagonize the effects of Ang-(1-7).
Methods: Sprague-Dawley rats underwent prolonged MV (8 h), while receiving an iv infusion of sterile saline 0.9% (vehicle) or Ang-(1-7) or Ang-(1-7) + A-779 or Ang-(1-7) + A-779 + PD123319. Diaphragms were collected for ex vivo contractility measurement (with electric stimulation), histological analysis, quantitative real-time PCR, and Western blot analysis.
Results: MV resulted in a significant reduction of diaphragmatic contractility in all groups of treatment. Ang-(1-7)-treated rats showed higher muscular fibers cross-sectional area and lower atrogin-1 and myogenin mRNA levels, compared to vehicle treatment. Treatment with the antagonists of Mas and Ang-II receptor 2 (AT2R) caused a significant reduction of muscular contractility and an increase of atrogin-1 and MuRF-1 mRNA levels, not affecting the cross-sectional fiber area and myogenin mRNA levels.
Conclusions: Systemic Ang-(1-7) administration during MV exerts a protective role on the muscular fibers of the diaphragm preserving muscular fibers anatomy, and reducing atrophy. The involvement of Mas and AT2R in the mechanism of action of Ang-(1-7) still remains controversial.
Databáze: MEDLINE
Externí odkaz: