Renal T cell infiltration occurs despite attenuation of development of hypertension with hydralazine in Envigo’s female Dahl rat maintained on a low-Na⁺diet

Abstract

Many studies have suggested that renal T cell infiltration contributes to the pathogenesis of salt-sensitive hypertension. To investigate this mechanism further, we determined T cell profiles in the kidney and lymphoid tissues as a function of blood pressure in the female Envigo Dahl salt-sensitive (SS) rat maintained on low-Na+ (LS) diet. Mean arterial pressure and heart rate were measured by telemetry in SS rats from 1 mo old (juvenile) to 4 mo old. Normotensive salt-resistant (SR) rats were included as controls. Frequencies of T helper (CD4+) cells were greater in the kidney, lymph nodes, and spleen in 4-mo-old hypertensive SS rats compared with normotensive SR animals and SS juvenile rats, suggesting that renal T cell infiltration contributes to hypertension in the SS rat on a LS diet. At 1.5 mo, half of the SS rats were treated with vehicle (Veh), and the rest received hydralazine (HDZ; 25 mg·kg−1·day−1) for 11 wk. HDZ impeded the development of hypertension compared with Veh-treated control rats [mean arterial pressure: 157 ± 4 mmHg in the Veh-treated group ( n = 6) vs. 133 ± 3 mmHg in the HDZ-treated group ( n = 7), P < 0.001] without impacting T helper cell frequencies in the tissues, suggesting that HDZ can overcome mechanisms of hypertension driven by renal T cell infiltration under the LS diet. Renal frequencies of CD4+CD25+ and CD4+CD25+FoxP3+ regulatory T cells were significantly higher in 4-mo-old hypertensive rats compared with normotensive SR rats and SS juvenile rats, suggesting that these T cell subpopulations play a compensatory role in the development of hypertension. Greater understanding of these T cell populations could lead to new therapeutic targets for treating inflammatory diseases associated with hypertension.

T cell-derived extracellular vesicles are elevated in essential HTN

“…These kidney-isolated EVs also correlated with SBP levels. As T cells have been implicated in sodium retention in the kidney during HTN and infiltrating the kidney in hypertensive animals (15,21), it remains to be determined whether leukocyte-derived EVs (CD45 + ) in the kidney come from the circulation or are generated in the kidney from infiltrating immune cells (24). Furthermore, our observation raises the question whether EVs in tissue are simply biomarkers or have direct functional role in mediating tissue injury or regulation of blood pressure.…”

Ovariectomy and high salt increase blood pressure and alter sodium transport proteins in peripheral blood mononuclear cells of adult Wistar rats

“…It is well established that innate and adaptive immunity participate in the pathogenesis of arterial HT (Guzik et al., 2007; Norlander et al., 2018). However, it is still unclear whether immune cells found in renal tissue, blood vessels or skin (Xiao et al., 2015; Mikolajczyk et al., 2016; Machnik et al., 2009) may induce HT development or whether the presence of immune cells is secondary to the increase in BP (Pai et al., 2019).…”