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.

Zambelli, V., Sigurtà, A., Rizzi, L., Zucca, L., Delvecchio, P., Bresciani, E., et al. (2019). Angiotensin-(1-7) exerts a protective action in a rat model of ventilator-induced diaphragmatic dysfunction. INTENSIVE CARE MEDICINE EXPERIMENTAL, 7(1) [10.1186/s40635-018-0218-x].

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

Zambelli, V;Sigurtà, A;Rizzi, L;Delvecchio, P;Bresciani, E;Torsello, A;Bellani, G
2019

Abstract

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.
Articolo in rivista - Articolo scientifico
Angiotensin-(1–7); Diaphragm; Ventilation;
English
2019
7
1
8
open
Zambelli, V., Sigurtà, A., Rizzi, L., Zucca, L., Delvecchio, P., Bresciani, E., et al. (2019). Angiotensin-(1-7) exerts a protective action in a rat model of ventilator-induced diaphragmatic dysfunction. INTENSIVE CARE MEDICINE EXPERIMENTAL, 7(1) [10.1186/s40635-018-0218-x].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10281/223125
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