PULMONARY CELL STAINED IN A RAT MODEL OF FAT EMBOLISM FOR RENIN AND PRORENIN ARE INCREASED AFTER ALISKIREN TREATMENT, WHICH AMELIORATES THE FAT‐INDUCED INFLAMMATORY PROCESS

Abstract

IntroductionFat Embolism (FE) induced in rats by IV injection of Triolein (T) results in pulmonary vasculitis, inflammation, and fibrosis (1). Captopril and losartan, two drugs acting on the renin angiotensin system, prevent this damage (2). Administration of the renin inhibitor aliskiren also ameliorates the lung's histopathological changes induced by T injections with findings present as early as 48 hours after injection (3). Aliskiren also reduced the number of mast cells observed after T injection (4). This study is aimed at assessing aliskiren's effect on both the presence of vasculitis and on the number of renin/prorenin stained cells in a rat model of FE.Materials and MethodsSprague‐Dawley rats (250–300g) were treated with 0.2 ml IV of T (n=18) or saline (n=4). One hour later the rats were divided into three groups with injections with 0.2 ml of saline, 50 mg/kg, and 100 mg/kg of aliskiren (n=6 per group). 48 hours later all subjects were necropsied after isoflurane anesthesia, lungs removed and fixed in 10% formalin with sections submitted for H&E, Trichrome, and Abscam specific antibodies for renin/prorenin cells (R/P). Two pathologists unaware of the slide identity took 10 photographs at random at 400× and counted the number of R/P stained cells.ResultsSections demonstrated lung arterial vasculitis, septal inflammation, and fibrosis which were evident after 48 hours. Renin‐Prorenin stained cells were present in all groups and mostly located in the arterial adventitia, the thickened septa and subpleura. R/P immunointense reactivity was observed in cells of different sizes and shapes; with some having small oval stained cytoplasm and nucleus, while others demonstrated larger cytoplasm and nucleus with less intense stain and diffuse cytoplasmic vacuoles. A significant increase was seen for the T‐saline group vs the controls (p=0.008) for the small cells, but not for the larger ones. The 50 mg dose of aliskiren did not reduce either cell numbers while the 100 mg dose however induced a marked reduction vs the T‐saline cells both for both small and large cells (p=0.007 and 0.012 respectively). The ratio of small vs large cells was approximately 75% vs 25% for all groups.ConclusionThe increase in R/P stained cells after FE may be related to an increase in pulmonary mast cell population as seen in other pathological conditions and underlines the RAS involvement in FE.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.