No abstract

Our previous studies using an Induction‐Delay‐Expression (IND‐DEL‐EXP) paradigm to study hypertensive response sensitization (HTRS) demonstrated that various challenges (stressors) including a subpressor dose of angiotensin (ANG) II given during IND, resulted in HTRS to a subsequent treatment with slow‐pressor dose of ANG II during EXP. The induction of HTRS is associated with upregulated expression of proinflammatory cytokines and the macrophage marker CD11b in the brain regions involved in blood pressure (BP) regulation including the lamina terminalis (LT) and paraventricular hypothalamic nucleus (PVN). In this study, we investigated whether brain macrophages are necessary for low‐dose ANG II‐induced HTRS. Depletion of brain macrophages was produced by feeding a colony‐stimulating factor 1 receptor (CSF1‐R) inhibitor, PLX3397 (75 mg/kg/d), beginning 1 week before starting IND and continuing the drug throughout the 1 week IND period. The results showed that in control condition, low‐dose ANG II (10 ng/kg/min) treatment during IND resulted in an enhanced hypertensive response to the subsequent slow‐pressor dose of ANG II (120 ng/kg/min) when compared to control animals with saline pretreatment during IND (Δ39.1±4.2 vs. Δ21.5±4.9 mmHg). Depletion of brain macrophages during IND slightly increased baseline BP, which came back after stopping feeding PLX3397 during DEL. However, the depletion of macrophages blocked HTRS induced by low‐dose ANG II given during IND (Δ25.8±4.3 mmHg). Immunohistochemistry confirmed the depletion of macrophages in the subfornical organ and PVN after feeding PLX3397. The results indicate that brain macrophages are necessary for the induction of HTRS.