Iba1+ microglia/macrophages in the rat hypothalamic paraventricular nucleus are both resident and bone marrow‐derived in Ang II induced hypertension (875.5)

We have previously demonstrated that Angiotensin II (Ang II)‐induced hypertension increases activated microglial cells in the hypothalamic paraventricular nucleus (PVN). The objective of this study was to determine whether the origin of these cells is, in part, bone marrow (BM). We investigated whether minocycline (Mino), an antibiotic that crosses the BBB, would attenuate the microglial/macrophage responses and thereby the Ang II‐dependent increase in blood pressure (BP). Methods: SD rats underwent BM ablation followed by reconstitution with whole BM from eGFP donors. Following a 3 month recovery, animals were randomized to receive SC saline + H2O; SC Ang II + H2O; or SC Ang II + oral Mino (50 mg/kg). BP was measured weekly by tail‐cuff (n=5 per group) for 7 weeks. Iba1 antibody was used to image and quantify microglia expressing GFP (n=3 per group). Results: The Ang II/H2O group showed increased mean arterial pressure (MAP; 178 ± 9 vs. 104 ± 2 mmHg; p<0.001) and 4.3‐fold increase in GFP+/Iba1+ cells (p<0.05) from Saline/H2O group. Oral Mino attenuated the increased MAP (121 ± 7 mmHg) and caused a 37% decrease in GFP+/Iba1+ cells in the PVN. Conclusion: These data demonstrate that AngII‐induced hypertension is associated with an increase in the BM‐derived microglia/macrophages in the PVN and oral Mino treatment attenuated both the hypertension and extravasation of BM cells into PVN. Grant Funding Source : This research is supported by NIH grant (HL 33610 to MKR).