Prevention of Vascular Congestion Improves Renal Recovery and Function Post Renal Ischemia‐Reperfusion in Male Spontaneous Hypertensive Rats

Abstract

Acute kidney injury (AKI) due to ischemia‐reperfusion (IR) is a serious and frequent complication in clinical settings and often progresses to kidney failure. The male gender is associated with greater severity and mortality following AKI, and young males have a greater prevalence of hypertension vs. age‐matched females. Despite the widespread prevalence of hypertension as a common co‐morbid condition with AKI, the impact of established hypertension on the progression of renal injury post‐AKI in either sex is poorly understood. Vascular congestion in the outer medulla is an early event occurring after IR, and congestion has been linked to worse renal outcomes following IR. The present study tested the hypothesis that increased vascular congestion in hypertensive males leads to impaired renal recovery compared to hypertensive females following renal IR. 13 wk old male and female normotensive Sprague Dawley rats (SD) and Spontaneous Hypertensive Rats (SHR) were subjected to sham or 25‐minute warm bilateral ischemia followed by reperfusion (n=6). Blood and urine were collected at 24 hrs and 7 days after IR; kidneys were harvested at 7 days for histological analysis. IR increased plasma creatinine (Pcr), BUN and proteinuria in all groups compared to respective sham controls at 24 hrs, with a sex difference in IR‐induced increases in Pcr observed in SD but not in SHR (SD Scr: Psex*IR<0.05; SHR Pcr: Psex*IR=0.4). At 7 days post‐IR, Pcr and BUN remained elevated only in male SHR compared to sham control (Pcr: PIR=0.03; BUN: PIR<0.05); Pcr and BUN returned to sham levels in all other groups. Histological examination of SHR kidneys at 7 days post‐IR showed sustained increases in vascular congestion (PIR=0.01; Psex*IR=0.002), damaged tubules (PIR=0.0003; Psex*IR=0.0019) and tubular cell apoptosis (P IR=0.001; Psex*IR=0.001) compared to sham controls in male SHR but not in females. Further, to study the role of IR induced vascular congestion on impaired recovery and loss of renal function in male SHR, additional SHR were pretreated with heparin (1500U/kg, n=6) prior to IR. Pre‐treatment with heparin prevented IR‐induced vascular congestion (PIR*Heparin=0.04) and tubular damage (PIR*Heparin=0.02) and improved renal function in male SHR 7 days post‐IR (Scr‐PIR*Heparin<0.05; BUN: PIR*Heparin=0.02) compared to heparin treated sham controls. Heparin pretreatment did not alter kidney function in female SHR 7 days post‐IR (Pcr‐PIR*Heparin=0.9; BUN: PIR*Heparin=0.2). In conclusion, our data demonstrated that persistent IR‐induced vascular congestion is a major driving factor to long‐term impaired renal recovery post IR in hypertensive males.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.