Abstract
Abstract 16566: CD161a-Positive Immune Cells Are Necessary for Cholinergic-Mediated Hypertension and Regulate Expression of Renal Sodium Transporters in a Genetic Model of Essential Hypertension
Circulation (New York, N.Y.), Vol.138(Suppl_1 Suppl 1), pp.A16566-A16566
11/06/2018
DOI: 10.1161/circ.138.suppl_1.16566
Abstract
IntroductionHypertension has traditionally been thought to involve the renal, vascular, and nervous systems. Recent experimental data have confirmed a role of the immune system and inflammation as key factors in the development of hypertension. The “neuro-immuno” axis describes a regulatory, bidirectional interaction between the autonomic nervous and immune system. Although the activation of nicotinic acetylcholine receptors (nAChRs) has been shown to mediate anti-inflammatory immune responses, our laboratory has shown that activation of nAChR in the Spontaneously Hypertensive Rat (SHR), a genetic model of essential hypertension, leads to expansion of a pro-inflammatory CD161a+/CD68+ M1 macrophage, renal inflammation, and the premature development of hypertension.HypothesisWe hypothesized that this “cholinergic mediated hypertension” is dependent on the pro-inflammatory CD161a-positive immune cell and involves alteration of expression of renal sodium transporters.MethodsTo investigate this hypothesis, young prehypertensive SHR underwent ablation of the CD161a-positive immune cells via intraperitoneal injection of a monoclonal antibody targeted against CD161a (n=5) or the isotype control immunoglobulin (IGG, n=5). Following ablation of the CD161a-positive immune cells, all animals were implanted with subcutaneous osmotic pumps to infuse nicotine (15mg/kg/day) for 14 days. Blood pressure was measured by tail-cuff twice weekly.ResultsAblation of CD161a-positive immune cells prevented the development of cholinergic mediated hypertension following nicotine infusion (126±2mmHg), compared to the control group receiving IGG (143±9mmHg)(p<0.05). Protein expression of the alpha and beta subunits of ENaC (epithelial sodium transporter), and NCC (sodium-chloride cotransporter) were reduced by 50% (p<0.0001), 60% (p<0.0001), and 50% (p<0.001), respectively, in response to ablation of CD161a+ immune cells, compared to IGG control. Alterations in the expression of renal sodium transporters was accompanied by a ~83% (p<0.05) and 59% (p<0.05) increase in random urinary sodium measurements and fractional excretion of sodium.ConclusionsWe conclude that CD161a-positive immune cells are involved in sodium reabsorption through regulation of expression of renal sodium transporters and are necessary for cholinergic mediated hypertension in SHR.
Details
- Title: Subtitle
- Abstract 16566: CD161a-Positive Immune Cells Are Necessary for Cholinergic-Mediated Hypertension and Regulate Expression of Renal Sodium Transporters in a Genetic Model of Essential Hypertension
- Creators
- Nandita Raikwar - University of IowaPeter SnyderFrancois AbboudSailesh Harwani
- Resource Type
- Abstract
- Publication Details
- Circulation (New York, N.Y.), Vol.138(Suppl_1 Suppl 1), pp.A16566-A16566
- Publisher
- by the American College of Cardiology Foundation and the American Heart Association, Inc
- DOI
- 10.1161/circ.138.suppl_1.16566
- ISSN
- 0009-7322
- eISSN
- 1524-4539
- Language
- English
- Date published
- 11/06/2018
- Academic Unit
- Fraternal Order of Eagles Diabetes Research Center; Cardiovascular Medicine; Molecular Physiology and Biophysics; Medicine Administration; Internal Medicine
- Record Identifier
- 9984362356102771
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