Female Spontaneous Hypertensive Rats (SHR) Have Better Recovery In Response To Renal Ischemia Reperfusion Injury Than Males

Abstract

Hypertension is a known risk factor for acute kidney injury (AKI) but there is little research on the link between the two. Normotensive males are considered to be more susceptible to AKI compared with females. However, how hypersensitive males and females respond to AKI is not well understood. The purpose of the present study is to test the hypothesis that male SHR have worse outcomes than females following renal ischemia reperfusion (IR). 13 week old male and female SHR were subjected to sham‐operated or 25‐minute warm bilateral ischemia followed by 7 days of reperfusion (n=5–6). Renal injury and function were assessed by the following methods: 1) plasma creatinine quantified by Quantichrome creatinine kit, 2) peritubular capillary congestion by Masson's trichrome staining, and 3) tubular damage by hematoxylin and eosin staining of kidney sections and Western blot analysis of kidney injury molecule‐1 (KIM‐1). 24 hours following IR, both male and female SHR showed a significant increase in plasma creatinine compared to respective sham‐operated controls, although the increase in creatinine was greater in males (males: 0.55±0.22 vs. 0.25 ±0.06 mg/dl; females: 0.45±0.06 vs. 0.26±0.06 mg/dl; PIR=0.02; Psex=0.3; Psex*IR=0.03). After 7 days of reperfusion, plasma creatinine remained elevated in male SHR compared to baseline (0.46±0.21 mg/dl vs 0.26±0.065), whereas plasma creatinine in female SHR returned to baseline levels (0.27±0.06 vs 0.26±0.06 mg/dl; PIR=0.03; Psex=0.05; Psex*IR=0.04). Further, histological examination of kidneys following 7 days of reperfusion showed a significant increase in the percentage of peritubular capillary congestion (male: 20±6% increase; female: 0% increase: PIR=0.642; Psex=0.018; Psex*IR=0.002) and damaged tubules (male: 42±13% increase; female: 6±3% increase; PIR=0.0001; Psex=0.0019; Psex*IR=0.0019) compared to sham controls only in males. KIM‐1 protein expression also remained significantly elevated in the outer medulla of both male and female SHR following 7 days of reperfusion, although levels were higher in males compared to female SHR (male: 0.779±0.012 vs 0.073±0.006; female: 0.240±0.147 vs 0.0374±0.038; PIR=0.0002; Psex=0.0092; Psex*IR=0.019). In conclusion, our data support the hypothesis that there is a sex difference in recovery from IR where female SHR recovered faster than male SHR. Further studies are ongoing in SHR to dissect the molecular mechanism(s) driving sex differences in IR outcomes.Support or Funding InformationThis work was supported by National Institute of Health (1P01HL134604‐01 to J.C. Sullivan)This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.