Pericytes are contractile cells that surround the renal vasa recta capillaries and are most densely populated in the outer medulla. Recent clinical trials have linked pericyte number to improved outcomes following transplant1, however, why pericytes are associated with improved graft survival remains unclear. Red blood cell (RBC) stasis is a hallmark of renal ischemia reperfusion (IR) injury. We hypothesize a novel function of renal medullary pericytes is ‘to help prevent RBC aggregation within the renal medulla following periods of ischemia and that reduced pericyte number will result in greater RBC aggregation following IR’. In order to test this hypothesis, we adapted a method previously reported2 to reduce pericyte number in male spontaneously hypertensive rats (SHR) involving transient treatment with an ACE inhibitor. 13 week old male and female SHR were studied. Rats pre-treated with enalapril (10 mg/kg/day in drinking water) from 5-9 weeks of age and controls (untreated) were subject to 45 min of warm (37oC) bilateral renal ischemic clamping prior to reperfusion (n=8-11). Rats were anesthetized with 2% isoflurane and administered buprenorphine (0.1 mg/kg) post-surgery as an analgesic. 24 hours later, rats were anesthetized using xylazine/ketamine (1:2 dilution; 0.2ml/0.2kg i.m.), tissues harvested and the animals humanly euthanized by pneumothorax. Excised kidneys were bisected, and placed in 10% formalin before sectioning. Trichrome stained renal sections were then scored (0 for no RBC occlusions – 4 for majority of vessels occluded) by an investigator blinded to the analysis. Immunocytochemistry with anti-neural glial 2 was performed to quantify pericytes. Two-way ANOVA was used for statistical analysis. Enalapril treatment resulted in a 15-20% reduction in pericyte number when compared to controls in both sexes (M: 4.6±0.3 vs. 3.8±0.4; F: 4.5±0.2 vs. 3.8±0.3; pTREATMENT=0.02). Reducing pericyte number with enalapril treatment significantly increased vasa recta clogging in both sexes after IR (M: 1.2±0.3 vs. 2.3±0.3; F: 1.1±0.3 vs. 1.7±0.3; pTREATMENT=0.02). Enalapril treatment also significantly increased peritubular clogging (M: 1.0±0.4 vs. 2.3±0.4; F: 2.1±0.4 vs. 2.4±0.3; pTREATMENT=0.03). There was a significant correlation between pericyte number and peritubular clogging in both males and females; furthermore, the slope was steeper in males (M: slope=-1.5, p=0.004; F: slope=-0.5, p=0.001). Our data indicate that pericyte number is strongly associated with RBC aggregation in the renal medulla following IR in rats and support the hypotheses that vasa recta pericytes may have a role in limiting RBC aggregation and vessel occlusion in the renal medulla.