Sex Differences in the Renal T Cell Profile in DOCA-Salt Hypertension are Independent of MR Activation and Increases in Blood Pressure

We previously reported that T cells contribute to sex differences in blood pressure (BP) in DOCA-salt hypertension, yet the mechanism(s) modulating T cell activation are still being investigated. The goal of the current study was to determine the relative contribution of mineralocorticoid receptor (MR) activation vs. increases in BP to changes in the renal T cell profile in male and female DOCA-salt rats. 10-week-old uni-nephrectomized male and female Sprague Dawley rats were implanted with a subcutaneous 21-day slow-release DOCA pellet (200 mg). To assess the relative contribution of MR activation vs. the development of hypertension, subsets of male and female DOCA rats were randomized to 1) saline vehicle (0.9% NaCl), 2) saline plus specific MR antagonist Eplerenone (100mg/kg/day), 3) saline plus BP lowering drugs hydrochlorothiazide and reserpine (HCTZ/Res) throughout 3-week DOCA treatment. BP was measured via radiotelemetry. Kidneys were harvested and processed for flow cytometry, biochemical, and histological analysis. Males exhibited greater increases in BP with DOCA than females. Eplerenone treatment attenuated DOCA-salt hypertension. Eplerenone significantly decreased pro-inflammatory Th17 cells and increased anti-inflammatory Tregs in both sexes, however sex differences in the renal T cell profile were largely maintained. To separate the effects of lowering BP from blocking MR inhibition, HCTZ/Res was employed to block DOCA-salt induced hypertension. HCTZ/Res also attenuated the pro-inflammatory renal T cells in DOCA-salt hypertension, and sex differences in renal T cells were largely maintained. These data suggest that neither MR activation nor elevation in BP mediates the sex differences in the renal T cell profile in DOCA-salt rats.