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Angiotensin II–Dependent Increase in the b=Bone Marrow Sympathetic Drive Initiates the Inflammatory and Endothelial progenitor Cell Imbalance and Precedes Blood Pressure Increase
Author(s) -
Ahmari Niousha,
Santisteban Monica,
Baekey David,
Raizada Mohan,
Zubcevic Jasenka
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1059.1
Subject(s) - endocrinology , medicine , progenitor cell , bone marrow , angiotensin ii , blood pressure , stem cell , biology , microbiology and biotechnology
Dysfunctional brain‐bone marrow (BM) communication is associated with overactive brain RAS, leading to elevated sympathetic drive (SNA) to the BM and increased blood pressure (BP). Here, we hypothesized that angiotensin II (Ang II)‐dependent increase in BM SNA directly initiates the endothelial progenitor (EPC) and inflammatory cell (IC) imbalance, independently of its effects on BP. Methods Subpressor dose of Ang II (15 ng/kg/min ICV) was infused in Sprague‐Dawley rats for 3, 7 and 21 days. The in situ decerebrated artificially‐perfused preparation was used to determine femoral BM SNA (fSNA) in control and Ang II rats. Fluorescence‐activated cell sorting (FACS) investigated the levels of EPCs and ICs in blood and BM. Results Electrophysiology revealed a 20% increase in the fSNA peak firing as early as 7 days of Ang II infusion. This was associated with elevation in BM IC levels (CD4 + :2fold; CD4 + .CD25 + :4fold; CD3 + :2fold; CD3 + .CD45 + :4fold; CD68 + :2fold) and EPCs (CD90 + :1.5fold). Femoral BM sympathectomy significantly decreased levels of Ang II‐dependent ICs but not EPCs in the BM. No change was observed in circulating cells at any time point. Conclusion These observations demonstrate that Ang II‐dependent increase in BM fSNA directly affects the BM EPC/IC balance, independent of the blood pressure effects. Thus, elevated BM fSNA may initiate early impaired BM activity, but additional prohypertensive signals may be needed for fully blown immune response and development of hypertension‐related pathophysiology. AHA 14SDG18300010.