Effect of Aliskiren on Fat Distribution and Elimination in the Lungs of Rats after Triolein‐induced Fat Embolism
Authors: Fletcher Amanda , Poisner Alan M , Ponnapureddy Rakesh , Arora Simran , Patel Chirag , Siddiqi Ahsan , Arif Dauod , Ho Andrea , Molteni Agostino 
Published: November 2023

Introduction

In a rat model of fat embolism (FE) induced by i.v. triolein (T), severe lung damage develops from 48 hours to 10 weeks post treatment; fat is differentially present in the lungs of these animals at different intervals of time.1,2,3 This damage is reduced by administration of the ACE 1 inhibitor, captopril, or the Ang type I receptor blocker, losartan one hour after T.2 Renin levels were increased in the lungs of these rats.4 To further evaluate the role of the renin‐angiotensin system (RAS) in the FE‐induced pulmonary pathology, we treated rats with aliskiren (Ali) (Tekturna), a direct renin inhibitor, and examined its effects on T‐induced fat accumulation.

Methods

After approval by UMKC IACUC, twenty‐two male Sprague‐Dawley rats (280–300 g) were divided into four groups. Number of animals per group and treatment regimens are summarized in table 1. All rats were sacrificed at 48 hours. After euthanasia and necropsy, a portion of the lung was frozen at −20°C and stained for fat using Oil Red O. Eight photographs per animal slide were taken at 100×, and the presence of fat was digitally analyzed and quantified by Image J.

Results

Saline injected controls (group A) had a minimal amount of fat present (mean 0.03% +/− SEM 0.02). Lungs of T + saline rats (group B) had a larger amount of fat (mean 3.95% +/− 1.04) present as small droplets diffused throughout the pulmonary interstitial space or as large droplets around peribronchial veins, confirming findings of our previous studies. Ali administration at both doses, group C (mean 1.79% +/− 0.35) and group D (mean 1.03% +/− 0.29), reduced the presence of fat. This difference was statistically significant compared to group B (p< 0.01), but not compared to the control values (Fig. 1). Fat droplets present in the rats treated with Ali were comparatively large in size and mostly located around peribronchial veins.

Conclusion

The decreased presence and limited distribution of the fat in Ali treated animals where the pathologic fibrotic and inflammatory processes were not evident may be related to faster elimination of the injected T or to intracellular processes related to the RAS. Questions to be determined include the optimal time to give Ali, the dose‐dependency of its effects at early and later times post‐fat injection and the role of the individual mediators of the RAS.

Support or Funding Information

1) This work was supported by a CTSA grant from NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research # TL1TR000120. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH or NCATS 2) Mary Katherine Geldmacher Research Foundation, St. Louis, MO

Treatment groups

Group
n
Day 0Time 0 hours
Day 0Time 1 hour
Day 2Time 48 hours

A
4
Saline 0.2 mL i.v.
Saline 0.2 mL i.p.
Euthanasia

B
6
Triolein 0.2 mL i.v.
Saline 0.2 mL i.p.
Euthanasia

C
6
Triolein 0.2 mL i.v.
Aliskiren 50 mg/kg i.p.
Euthanasia

D
6
Triolein 0.2 mL i.v.
Aliskiren 100 mg/kg i.p.
Euthanasia