Abstract 18617: Is Genetic Hypertension Immunologically Mediated and Adoptively Transferrable by Bone Marrow From the Spontaneously Hypertensive Rat?
We have recently reported that a proinflammatory state of the innate immune system may contribute to genetic hypertension in the spontaneously hypertensive rat (SHR). In these experiments we contrasted the population of immune cells from SHR and from the normotensive control WKY, and tested the hypothesis that the hematopoietic system of SHR is prohypertensive when adoptively transferred to a normotensive F1 hybrid (WKY x SHR) rat. We performed immuno-phenotyping of splenocytes from the day of birth to 38 weeks. A specific subset of CD161+ splenocytes, which was sparsely seen in WKY (<1%) at any age, was increased at birth in SHR to a level of 5% and progressively increased to 10, 20 and 30% at 5, 20, and 38 weeks of age respectively. CD161+ cells are characteristically Th17 cells, NK cells, and dendritic cells that overexpress retinoic acid related orphan receptor gamma (RORγt) and IL-17, a pro-inflammatory prohypertensive cytokine. We also transfused bone marrow from 5-week-old male WKY or SHR into 5-week-old F1 hybrid rats (WKY x SHR) that had been sub-lethally irradiated (9-12 Gy). Blood pressure (tail cuff) of the recipient F1 rats was measured after transplantation. Early results indicate that at 2, 5 and 7 weeks after transfer, the systolic pressure averaged 140±2, 152±8, and 150±5 mmHg (n=4) in F1 recipients of WKY marrow, respectively. Corresponding values in F1 recipients of SHR marrow were 150±5, 158±5, and 169±6 mm Hg (n=4). We conclude that 1) SHR exhibit a much higher abundance of proinflammatory CD161+ immune cells than WKY beginning prior to the onset of hypertension and progressively increasing with age, and 2) Preliminary results suggest that genetic hypertension may be adoptively transferred with bone marrow from SHR and not WKY rats.
- © 2013 by American Heart Association, Inc.