Abstract 111: Elevated Sympathetic Drive to the Bone Marrow Contributes to the Inflammatory Response and Dysfunctional Endothelial Progenitor Cells in the Spontaneously Hypertensive Rat
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. Thus, imbalanced EPC/IC ratio, coupled with dysfunctional EPCs, are key in the vascular pathophysiology of hypertension. We demonstrated that SHR, which have elevated sympathetic drive, exhibit a significantly lower BM EPC/IC ratio due to lower EPCs and higher ICs. The inverse relationship between the sympathetic drive and EPC/IC ratio is supported by our data showing that elevation in the overall sympathetic drive in the WKY, as a result of the light:dark cycle, decreases the EPC/IC ratio. This has led us to propose that the SHR exhibit chronically elevated sympathetic drive to the BM, which contributes to the impaired EPC/IC ratio and EPC dysfunction.
Methods: Femur from 21-week old SHRs (MAP=∼145 mmHg) and WKYs (MAP=∼100 mmHg) were used to determine norepinephrine (NE) and tyrosine hydroxylase (TH) levels. Femur BMs were flushed, and cell supernatants collected for NE measurements (ELISA). Femurs from a separate group of rats were fixed and used for TH quantification (IHC). Additional WKY and SHR were used for BM injection of GFP-tagged pseudorabies virus (GFP-PRV) to compare the extent of retrograde labeling from the femur BM to the brain autonomic areas (SFO, PVN, RVLM, NTS).
Results: We observed a ∼80% higher NE levels, and a ∼2.1 fold higher TH density, in the BM of SHR compared to WKY. This was accompanied by a ∼52% decrease in EPC/IC ratio and a ∼44% decrease in EPC function in the SHR compared to the WKY. Additional evidence for the increased sympathetic communication between the SHR autonomic brain areas and the BM was provided by PRV-GFP retrotracing. The data showed a profound labeling of the PVN neurons in the SHR compared to WKY, 7 days post-PRV-GFP injection. Less significant labeling was observed in other autonomic areas (RVLM>NTS>SFO) under similar conditions.
Conclusion: These observations demonstrate, for the first time, that there is an elevated sympathetic drive to the BM in the SHR. This is associated with an impaired BM activity, reflecting a decrease in EPCs and increase in ICs, which may contribute to the vascular pathophysiology in neurogenic hypertension.
- © 2012 by American Heart Association, Inc.