Persistent vascular congestion in male spontaneously hypertensive rats contributes to delayed recovery of renal function following ischemia-reperfusion compared to females.

Acute kidney injury (AKI) is a serious and frequent clinical complication with mortality rates up to 80%. Vascular congestion in the renal outer medulla occurs early after ischemia reperfusion (IR) injury, and congestion has been linked to worsened outcomes following IR. There is evidence implicating both male sex and preexisting hypertension as risk factors for poor outcomes following IR. The present study tested the hypothesis that male spontaneously hypertensive rats (SHR) have greater vascular congestion and impaired renal recovery following renal IR vs. female SHR and normotensive male Sprague-Dawley rats (SD). 13 wk old male and female SHR and SD were subjected to sham surgery or 30 minutes of warm bilateral ischemia followed by reperfusion. Rats were euthanized 24 hours or 7 days post-IR. IR increased renal injury in all groups vs. sham controls at 24 hours. At 7 days post-IR, injury remained elevated only in male SHR. Histological examination of SD and SHR kidneys 24 hours post-IR showed vascular congestion in males and females. Vascular congestion was sustained only in male SHR 7 days post-IR. To assess the role of vascular congestion on impaired recovery following IR, additional male and female SHR were pretreated with heparin (200 U/kg) prior to IR. Heparin pre-treatment reduced IR-induced congestion and improved renal function in male SHR 7 days post-IR. Interestingly, preventing increases in BP in male SHR did not alter sustained vascular congestion. Our data demonstrate that IR-induced vascular congestion is a major driving factor for impaired renal recovery in male SHR.