Minimal effect of aliskiren on renal vascular effects of fat embolism in an acute rat model
Authors: Khalafi Farzad , Elsherbiny Hisham , Vaidyanathan Vaishnavi , Ahmad Yembur , Poisner Alan , Molteni Agostino 
Published: November 2023

Introduction

In a rat model of fat embolism (FE) induced by injection of triolein (T), a severe inflammatory reaction leads to vasoconstriction and pulmonary fibrosis (1). Lung damage is already evident at 48 hrs, and after partial resolution, a second phase of increasing severity develops up to 10 weeks. (2) The renin angiotensin system (RAS) is involved in the process: administration of captopril and losartan prevents the acute inflammatory response and fibrotic process in the lungs (3) and the direct renin inhibitor aliskiren (ALI) also protects the lungs from vasculitis, and fibrotic change in an early phase (48 hrs) (4). We extended the study of ALI to the kidneys by evaluating the renal arterial response to T treatment in this model of FE.

Methods

22 Sprague Dawley rats received T (0.2 ml IV, n=18) or saline (n=4). The T treated rats were divided into three groups of 6 rats each and injected IP one hour later with 0.2 ml saline, ALI 50mg/kg or ALI 100mg/kg. Four controls received saline. Rats were killed 48 hrs later; the organs fixed and stained with H&E. Trichrome stain was used for fibrosis evaluation.

The vascular evaluation included lumen patency (LP) and media adventitia ratio (MAR), a marker of edema. LP was determined by the ratio of luminal internal diameter of the media vs. its external diameter. MAR was measured by the external medial diameter vs. external adventitia diameter. 10 photos at 400 X were taken by two pathologists unaware of the slide identity. Two photos at 100 X were also taken in each slide for evaluation of fibrosis. In addition to this evaluation, we also divided the arteries into two groups: small caliber with diameter of <150 mm (mostly located in the cortical section) and the larger caliber >150 mm (mostly present in tubuli).

Results

No significant difference was observed for the LP in any of the treatments, P=0.8669. However there was a significant effect on the MAR when all the arteries were considered, P=0.0007. The statistical difference in the MAR was due to effects on the larger arteries >150 mm with P=0.0033 with no differences in the small arteries. Renal fibrosis was minimal with the same amount in each group, mostly located around the arteries.

Conclusion

These findings were different than our observations in the lungs where statistical significance was observed in LP of the T treated rats vs. controls, and the 50 mg ALI treated rats. Fibrosis was severe in the lungs with damage mostly located around the small caliber arteries. The study suggests that the influence of the RAS on renal arteries after FE may be different from those in the lungs or that the course of time changes is different in the two organs. Nevertheless, ALI treatment did show protection against effects of T on the media adventitia ratio implicating the RAS in some effects of FE on the kidney at 48 hrs.

Support or Funding Information

Mary Katherine Geldmacher Research Foundation, St Louis MO.