Beschreibung:
<jats:p>In humans, early life stress (ELS) is a newly recognized cardiovascular disease risk factor and associated with increases in inflammation and risk of hypertension. Utilizing a rat model of ELS, maternal separation (MatSep), we recently reported that MatSep induced immune activation in the kidney compared to normally‐reared control animals. Chronic nitric oxide synthase blockade with LNAME in the drinking water is a model of hypertension with increased immune cells and inflammation. Therefore, we hypothesized that exposure to MatSep during early life and LNAME during adulthood would induce increased levels of renal injury markers and immune cells when compared to normally‐reared rats with LNAME during adulthood. MatSep involves separating rat pups from the dam for 3hrs/day from postnatal day 2 (PD2) to PD14. Normally‐reared littermate rats were used as controls. Twelve weeks old adult (n=6–8rats/group) control and MatSep rats were given LNAME (100mg/kg/rat) in drinking water for 7 days. LNAME was adjusted daily based on the amount of water intake. We compared urinary renal damage markers and renal immune cell populations in control and MatSep rats after LNAME treatment. On day 7 after LNAME, urine was collected for assessment of glomerular (albumin and nephrin) and tubular (KIM1 and NGAL) injury markers by enzyme‐linked immunosorbent assay (ELISA). Our results showed that urinary KIM1 excretion was significantly lower in MatSep rats compared to control rats (control LNAME vs. MatSep LNAME: 6.78mg/day ± 0.32 vs. 5.53mg/day ± 0.36; p = 0.029). No statistical differences were observed in urinary NGAL, albumin and nephrin excretion. At day 7 after LNAME, blood and kidneys were used for determination of immune cell populations by flow cytometry. The proportion of renal total T cells, T helper cells, macrophages, neutrophils, natural killer, and dendritic cells were similar in control and MatSep rats. However, there was a trend towards an increase in the proportion of cytotoxic T cells in MatSep compared to control animals (%CD45<jats:sup>+</jats:sup> cells; control LAME vs. MatSep LNAME: 14.04 ± 0.97 vs. 17.37 ± 1.35; p = 0.087). No differences were observed in the proportion of circulating immune T helper cells, cytotoxic T cells, macrophages, neutrophils, natural killer, and dendritic cells in control and MatSep rats. Our findings suggest that MatSep during early life may protect from tubular injury in response to inhibition of nitric oxide synthase. Future studies are warranted to determine whether the observed renal tubular protection is linked to LNAME induced blood pressure elevation, loss of tubular nitric oxide production, and T cell activation.</jats:p><jats:p><jats:bold>Support or Funding Information</jats:bold></jats:p><jats:p>Funded by Cardiovascular Pathophysiology NIH/NHLBI T32HL007918‐19 to IEO, R01DK059600 to JFG, and P01HL69999 to JSP.</jats:p><jats:p>This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in <jats:italic>The FASEB Journal</jats:italic>.</jats:p>