Abstract P111: Renal Perfusion Pressure Determines Renal Leukocyte Infiltration During Angiotensin II-Induced Hypertension in Sprague Dawley Rats

Abstract

A large body of work demonstrates an important role of renal infiltrating leukocytes in the development of hypertension and end-organ damage. We recently reported that the renal leukocyte infiltration during high salt-induced hypertension in Dahl Salt Sensitive (SS) rats was dependent on the elevated renal perfusion pressure (RPP). Here we performed studies to determine if the observed effects were limited to the Dahl SS rat and to separate out the effect of the high salt diet. We report here that renal leukocyte infiltration during Angiotensin II-induced (AngII) hypertension in rats is mediated by an increased RPP. Male Sprague-Dawley rats (n = 6) were maintained on a 0.4% NaCl diet throughout the study. At 9 weeks of age, rats were instrumented with carotid and femoral arterial catheters for measuring blood pressure (BP), a femoral venous catheter for AngII infusion, and a balloon occluder cuff was placed around the abdominal aorta between the renal arteries. The carotid and the femoral mean arterial pressures were used as surrogates for the RPP of the right and left kidneys respectively. After 7 days of recovery, baseline BP was measured for 3 days, then the rats were infused with AngII (50 ng/kg/min) for 7 days to induce hypertension. A computer-driven servo-control system was used to inflate the aortic cuff to maintain left RPP at baseline levels while right RPP was uncontrolled. Following 7 days of Ang II infusion, kidneys were removed to assess leukocyte infiltration by flow cytometry, and animals were euthanized. Baseline RPP was similar between right and left kidneys (115.6±3.9 vs 110.5±4.3 mmHg respectively). However, following 7 days of AngII infusion, the right RPP was significantly higher than left RPP (164.7±9.9 vs 112.5 ± 4.2 mmHg; respectively p<0.001). Significantly greater numbers of infiltrated leukocytes were found in the right compared to the left kidney (1.00±0.24 vs 0.53±0.10 X10 7 CD45+cells/kidney p=0.04) and assessment of the subsets found greater numbers of T cells (CD3+), B cells (CD45R+) and monocytes/macrophages (CD11b/c+) in the right kidney compared to the servo-controlled left kidney. The findings from these studies strongly support a critical role for RPP in renal leukocyte infiltration during AngII hypertension in rats fed low salt.