MINIMAL EFFECT OF ALISKIREN ON MAST CELLS COUNT AND RENAL VASCULAR DAMAGE IN ACUTE RAT MODEL OF TRIOLEIN INDUCED PULMONARY FAT EMBOLISM.

Abstract

IntroductionIn a rat model of fat embolism (FE) induced by injection of triolein (T) a severe inflammatory reaction leads to vasoconstriction and pulmonary fibrosis (1). Mast cell numbers are significantly increased in the lungs of the treated animals (2), and mast cell inhibition improves pulmonary vascular remodeling in pulmonary hypertension (3).There is evidence that the renin angiotensin system (RAS) is involved since drugs related to this system: captopril, losartan and aliskiren, prevent the pulmonary vasculitis and fibrosis in the early phase (48 hours) (4,5). However, aliskiren (ALI), a direct renin inhibitor, had a minimal effect on renal vasculitis, and fibrotic changes (6). In this study we evaluated the effect of T and ALI on renal mast cells.Materials and methods22 Sprague Dawley rates (250–300g BW) received T (0.2 ml n=18) or saline n=4. The T treated rats, divided into 3 groups of 6 each, were IP injected one hour later either with 0.2 ml saline, ALI 50 mg/kg or AL I 100 mg/kg. Four controls received saline.48 hours later rats were killed under isoflurane anesthesia and the kidneys and lungs stained with H&E, Trichrome, SMA1 for inflammation and fibrosis, and CD117 for mast cells. 10 photographs at 200× were taken for slides of each organ by two pathologists unaware of the slides' identity, mast cells were counted and pathological damage evaluated.ResultsRenal fibrosis and vasculitis were irrelevant by observation with all SM1, Trichrome or H&E stains, with the exception of the media adventitia ratio (MAR) of arteries (p= 0.007) which significantly increased after T‐saline treatment but not after ALI administration. These findings are in contrast with the observations of the lungs where the damage was severe and reduced by both ALI doses. Kidneys of ALI 100 mg/kg treated rats were similar to those ones of T+Saline or of the controls. Although a mild mast cell increase was noted in kidneys of T+Saline treated animals, no statistically significant difference in mast cells was observed.ConclusionRenal findings were quite different from our lung findings in either histopathological damage or mast cell accumulation. The study suggests that the RAS system influence on the kidneys differs from that of the lung at this acute stage of fat embolism.Support or Funding InformationSupported by the Catherine T Geldmacher Foundation, St. Louis, MOThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.