Premium
Abnormal autonomic regulation of the immune system in genetic hypertension
Author(s) -
Harwani Sailesh Chandur,
Chapleau Mark W,
Abboud Francois M
Publication year - 2011
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.25.1_supplement.640.34
Dysregulation of the autonomic nervous system represents a significant risk factor for cardiovascular mortality. Moreover, inflammatory responses involving T‐lymphocytes have been implicated in the development of genetic hypertension in the spontaneously hypertensive rat (SHR). We tested the hypothesis that autonomic dysregulation of the innate immune system contributes to the inflammatory response in SHR. Cytokine levels were measured in response to activation of Toll‐like Receptors (TLR) 7/8 and 9 in six individual splenocyte cultures from 5 week old (pre‐hypertensive) SHR (n=2) and WKY (n=2). We also measured the effects of Angiotensin II (Ang II, 1 μm) and Nicotine (10 μm) on responses to the TLR ligands. Increases in IL‐6 ranged from 2–6.5 ng/mLwith graded ligand doses. Nicotine pre‐treatment attenuated IL‐6 induction by 30 to 96% in WKY and, conversely, enhanced IL‐6 responses in SHR by 30–153%. Ang II pretreatment also enhanced IL‐6 responses in SHR vs. WKY. However, IL‐10 and TNFα levels did not differ significantly in WKY and SHR. In hypertensive SHR (16–17 weeks old), Nicotine and Ang II pretreatment enhanced IL‐6 responses in SHR. The results support the novel concept that an intrinsic autonomic dysregulation of the immune system is part of the pathogenesis of genetic hypertension. Targeted therapeutic intervention to restore the nicotinic anti‐inflammatory response and/or suppress the pro‐inflammatory response to both nicotine and Ang II may prove beneficial. (NIH HL14388)