Abstract 606: Reconstitution Of Bone Marrow With WKY Cells Lowers Central/Peripheral Inflammation And Blood Pressure In The SHR

Abstract

Introduction: Bone marrow (BM) is a crucial meeting point for the sympathetic innervation and hematopoietic/stem cells, including the inflammatory cells (ICs). However, the role of the BM in hypertension is not well defined. We recently demonstrated that a dysfunctional brain-bone marrow communication in rat models of neurogenic hypertension may be associated with impaired BM activity, characterized by elevated levels of ICs in the blood and BM when compared to the normotensive controls. Therefore, we hypothesized that BM of the spontaneously hypertensive rat (SHR) is pro-inflammatory, and that it contributes to hypertension in this rat model. Methods: 6-week old female SHR rats underwent BM ablation via a lethal dose of gamma ray irradiation (950 Rads), followed by reconstitution with whole BM mononuclear cells (MNCs, 10E6 cells per rat), derived from the BM of either SHR or WKY male rats (naïve SHR n=7; SHR-SHR n=11; SHR-WKY n=9). Following a three-month recovery period, BM reconstitution was confirmed by Y-chromosome FISH in blood MNCs. Blood pressure was measured by tail-cuff plethysmography. Blood was collected for isolation of MNCs, and quantification of T-cells (CD4/CD8 + ) was carried out by flow cytometry. Brains were collected and immunohistochemistry was performed using the microglial specific marker Iba1. Microglial activation was quantified by number of microglia per 40,000um 2 in the paraventricular nucleus (PVN) of the hypothalamus. Results: We observed no significant difference in the mean arterial pressures (MAP) between the naïve SHR (MAP= 134 ± 5 mmHg) and the SHR-SHR groups (MAP = 137 ± 5 mmHg). However, the SHR-WKY group showed an approximate 10% decrease in MAP, to 119 ± 4 mmHg (p<0.05). This was accompanied by a 30% decrease in the circulating T-cell levels, and a 20% decrease in activated microglial cells in the PVN of the SHR-WKY when compared to the SHR-SHR group (p<0.05). Conclusions: These data suggest that the pro-inflammatory properties of the SHR BM contribute to hypertension by increasing both the peripheral and central inflammatory status in the SHR. These observations support the role of the BM in hypertension, especially in affecting the inflammatory status, which is a hallmark of hypertension in the SHR.