Aliskiren Effect on Kidney Renin‐Prorenin Stained Cells in a Rat Model for Fat Embolism

The renin angiotensin system (RAS) is involved in the control of blood pressure through its action on the kidney and the treatment by the direct renin inhibitor Aliskiren (Ali) reduces it. We have previously shown in a rat model of fat embolism (FE) that triolein (T) injection leads to a severe inflammatory pulmonary reaction that causes fibrosis in lungs and Ali rescues it. We extended this study to the kidney by evaluating the renin/prorenin (R/P) presence in the kidney with and without Ali in a rat model of fat embolism. Methods Sprague Dawley rats (280–300 grams) were injected with T (0.2 ml IV, n=18) or saline (n=4) through tail vein. The T treated rats were divided into three groups of 6 rats each and one hour later injected with 0.2 ml saline, Ali 50mg/kg or Ali 100mg/kg while 4 controls received saline. After 48 hours, rats were euthanized, the kidneys were dissected out and fixed in 10 % formalin, sectioned and later immunostained for R/P specific antibody (from Abcam). Two pathologists unaware of the slide identity took 10 random images. R/P immunostained cells were quantified by using ImageJ program on medulla and cortical regions where the glomeruli were evident. Results In contrast to our previous results in the lungs of the same animals, the renal sections showed a minimal inflammatory damage without significant vasculitis and fibrosis. There are multiple cells cortical, tubular and glomerular showing the R/P cells immunostaining. It was evident by quantification of these cells by Image J that treatment with saline, T + saline, and T+ Ali resulted in an increase of R/P positive cells versus the saline + saline group but there was no statistically significant difference. However, in the glomeruli of the cortical region, R/P staining was mostly confined in the juxtaglomeruli of saline + saline and T+ saline groups and treatment with both doses of Ali reduced it and was statistically significant. Conclusion As previously reported for lungs and hearts, R/P positive cells were also present in kidneys. However in kidney, marked differences in several regions were seen after Ali administration. Furthermore, by reducing the R/P evaluation only to glomeruli, the study confirms that Ali pharmacological activity is interacting with the RAS system, and the drug has a potential use for the treatment of the respiratory distress syndrome consequent to the occurrence of fat embolism. Support or Funding Information Supported by Mary Katherine Geldmacher Research Foundation, St. Louis MO. This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .