Renin and Prorenin Stained Cells in the Hearts of Rats Subjected to Fat Embolism and Treated with Aliskiren, a Drug Ameliorating the Pulmonary Inflammatory Process
Authors: Arif Dauod , Colson Jordan , Al‐Husseinawi Ethar , Khalafi Farnaz , Ponnapureddy Rakesh , Pour Mohammad , Silswal Neerupma , Mudar Ismail , Leupold Bradley , Poisner Alan , Molteni Agostino 
Published: June 2021

Introduction

Fat embolism (FE) induced in rats by iv injection of triolein (T) caused pulmonary inflammation, fibrosis and vasculitis (1). Administration of renin inhibitor aliskiren ameliorates these organs histopathological damage as early as 48 hours after the injection (2). It also reduces the pulmonary number of the mast cells, a possible inflammatory mediator (3). The hearts of the same animals however showed only a mild but statistically significant increase of SMA1 (P<.005) at this interval time without vasculitis and inflammation (4) and without reduction of mast cells (5).

Pulmonary expression of renin/prorenin stained cells is also increased after T injection and it may be potentially related to the parallel mast cells increase (6). However, only the higher dose of aliskiren induced a reduction of these stained sells after T treatment (7).

Study is aimed at assessing aliskiren effect on both vasculitis and number of renin/prorenin stained cells in the hearts of the same T treated animals.

Methods

Sprague‐Dawley rats (250–300g) were treated with 0.2 ml iv of T (n=18) or saline (n=4). One hour later the injected rats were divided into three groups each of them receiving ip 0.2 ml of saline, 50 mg/kg, and 100 mg/kg of aliskiren (n=6 per group). Saline injected rats received 0.2 ml of saline. 48 hours later all subjects were necropsied after isoflurane anesthesia, hearts removed and fixed in 10% formalin with sections submitted for H&E Trichrome and an Abscam specific antibodies for renin/prorenin stained 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.

Results

Heart sections demonstrated collections of myocardial fibrils of uniform size and shape without significant inflammation or necrosis. The R/P immunostain highlighted the presence of multiple cells of varying sizes which were primarily allocated in the endocardial and subendocardial surfaces. None of the cells were seen in adventitia of coronary arteries thus showing difference with their location in lungs. Some animals had large number of myocardial R/P cells others had very few, statistically creating, a large standard deviation. Increase of R/P cells was seen after T injection with even more cells after aliskiren treatment in addition to T. The increase was related to their different aliskiren doses. So that after 100 mg of aliskiren +T the cells were twice as many as those ones of controls (192 +/− 84 SD vs 104 +/− 59). The large standard deviation did not make the difference significant.

Conclusions

The study confirms the previously reported histopathological difference of the T induced damage of lungs and hearts. Size and shape of the cells are similar in both organs. Location varies. R/P cells increase both in hearts and lungs after T injection and their location differs. Aliskiren didn't reduce in the heart the R/P cells number as seen in the lungs of the same treated animals. Such difference may be related to a different organ response to their renin angiotensin system.

Support or Funding Information

Catherine T Geldmacher Foundation, St. Louis, MO

This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.