Abnormal immune cell populations in SHR hypertension

Abstract

We have found that autonomic modulator of the immune system is abnormally proinflammatory in the spontaneously hypertensive rats (SHR) and may contribute to hypertension. Nicotine activates cholinergic receptors on splenocytes and suppresses IL‐6 release in response to TLR ligands in Wistar‐Kyoto (WKY) controls, but enhances it in pre‐hypertensive SHR. The objective of this study was to test (1) whether immune cell populations change as SHR age and (2) whether nicotine influences immune cell populations in SHR. We performed immuno‐phenotyping of splenocytes from WKY and SHR at ages ranging from 0 days to 38 weeks. In 0‐day‐old SHR splenocytes, a specific subset of cells (CD161+) was significantly higher than in WKY. The CD161+ cell population increased with age in SHR reaching 30% of the lymphocyte population. Infusion of nicotine increased the of CD161+ splenocytes in SHR but not in WKY. CD161+ cells produce IL‐17, a pro‐inflammatory cytokine involved in hypertension. Upon induction by phorbol myristate acetate and ionomycin, expression of IL‐17 mRNA was increased to a greater extent in SHR vs. WKY splenocytes. We conclude: 1) SHR exhibit a developmentally high abundance of CD161+ immune cells that increases with age as hypertension develops, and (2) nicotine selectively increases the number of potentially IL‐17‐producing CD161+ splenocytes in SHR. To our knowledge, this is the first demonstration of an age‐related increase in a specific immune cell population (CD161+) in genetic hypertension. Funded by NIH PPG HL14388.