Renal inflammation contributes to the pathophysiology of hypertension. CD161a+ immune cells are dominant in the Spontaneously Hypertensive Rat (SHR) and expand in response to nicotinic cholinergic activation.
We aimed to phenotype CD161a+ immune cells in pre-hypertensive SHR following cholinergic activation with nicotine, and determine if these cells are involved in renal inflammation and the development of hypertension.
Studies utilized young SHR and Wistar Kyoto (WKY) rats. Splenocytes and bone marrow cells were exposed to nicotine ex-vivo and nicotine was infused in-vivo. Blood pressures, kidney, serum, and urine were obtained. Flow cytometry, Luminex/ELISA, immunohistochemistry, confocal microscopy, and Western blot were used. Nicotinic cholinergic activation induced proliferation of CD161a+/CD68+ macrophages in SHR-derived splenocytes, their renal infiltration, and premature hypertension in SHR. These changes were associated with increased renal expression of monocyte-chemoattractant-protein-1 (MCP-1) and very-late-antigen-4 (VLA-4). Lectin-Like-Transcript 1 (LLT1), the ligand for CD161a, was overexpressed in SHR kidney, while vascular cellular (VCAM-1) and intracellular adhesion molecules (ICAM-1) were similar to WKY. Inflammatory cytokines were elevated in SHR kidney and urine following nicotine infusion. Nicotine mediated renal macrophage infiltration/inflammation was enhanced in denervated kidneys, not explained by angiotensin-II levels or expression of angiotensin type-1/2 receptors. Moreover, expression of the anti-inflammatory 7-nicotinic-acetylcholine receptor was similar in young SHR and WKY.
A novel, inherited nicotinic cholinergic inflammatory effect exists in young SHR, measured by expansion of CD161a+/CD68+ macrophages. This leads to renal inflammation and premature hypertension, which may be partially explained by increased renal expression of LLT-1, MCP-1, and VLA-4.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Biochemistry, Genetics and Molecular Biology
1
3%
Other
2
6%
Unknown
10
28%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 4. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 13 May 2017.
All research outputs
#11,454,403
of 34,343,841 outputs
Outputs from Circulation Research
#4,856
of 9,392 outputs
Outputs of similar age
#119,639
of 333,129 outputs
Outputs of similar age from Circulation Research
#35
of 84 outputs
Altmetric has tracked 34,343,841 research outputs across all sources so far. This one has received more attention than most of these and is in the 65th percentile.
So far Altmetric has tracked 9,392 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 12.8. This one is in the 47th percentile – i.e., 47% of its peers scored the same or lower than it.
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We're also able to compare this research output to 84 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 55% of its contemporaries.
