Introduction: Bone marrow (BM)-derived endothelial progenitor cells (EPCs) contribute to the repair of vasculature, whereas the inflammatory cells (ICs) contribute to the vascular damage. Recently, dysfunctional brain-BM communication has been associated with an impaired BM activity, reflecting a decrease in EPCs and increase in ICs. We hypothesized that an overactive brain RAS leads to elevated sympathetic drive to the BM, which precedes the increase in blood pressure (BP), initiates the EPC/IC imbalance, and contributes to the development of vascular pathophysiology.
Methods: Sprague-Dawley (SD) rats were infused with 15ng/kg/min Ang II ICV for 7 days. Following this, indirect BP measurements were taken, and the in situ decerebrated artificially-perfused preparation (DAPR) was used to compare thoracic (tSNA) and femoral BM sympathetic nerve activity (fSNA) between control and Ang II rats. In order to characterize tSNA and fSNA, we monitored the effects of elevated CO2 (9%) on the phrenic nerve activity (PNA), tSNA and fSNA. PNA-triggered averaging of integrated tSNA and fSNA signals was performed across 100 phrenic cycles, allowing for quantification of averaged tSNA and fSNA during discrete phases of the respiratory cycle: inspiration (I), post-inspiration (P-I), mid-expiration (M-E) and late expiration (L-E). Thus, the peak levels of tSNA and fSNA during each respiratory phase could be compared across preparations.
Results: We observed no differences in the BPs of control (95±5 mm Hg) and Ang II rats (96±2 mm Hg). Electrophysiology revealed a characteristic PNA pattern, and peak activity of tSNA and fSNA during the P-I phase, typical of the respiratory-sympathetic coupling. Exposure to 9% CO2 elevated both the tSNA and fSNA in the control and Ang II rats. However, a 75% increase in the tSNA peak firing, and a 20% increase in the fSNA peak firing were observed in the Ang II rats when compared to the control.
Conclusion: These observations demonstrate, for the first time, that elevated brain Ang II, at sub-pressor conditions, results in an increased sympathetic drive to the BM. This may initiate early impaired BM activity, reflecting in an imbalance in BM EPCs and ICs, which may contribute to the development of hypertension-related pathophysiology.