Renal Denervation and CD161a Immune Ablation Prevent Cholinergic Hypertension and Renal Sodium Retention

Article: Renal Denervation and CD161a Immune Ablation Prevent Cholinergic Hypertension and Renal Sodium Retention

Authors: Nandita S Raikwar, Cameron Braverman, Peter M. Snyder, Robert A. Fenton, David K. Meyerholz, Francois M. Abboud, and Sailesh C. Harwani

Journal: Am J Physiol Heart Circ Physiol. 2019 Jun 7. doi: 10.1152/ajpheart.00234.2019. [Epub ahead of print]

Abstract:
RATIONALE: Cholinergic receptor activation leads to premature development of hypertension and infiltration of pro-inflammatory CD161a+/CD68+ M1 macrophages into the renal medulla. Renal inflammation is implicated in renal sodium retention and the development of hypertension. Renal denervation is known to decrease renal inflammation.

OBJECTIVE: To determine the role of CD161a+/CD68+ macrophages and renal sympathetic nerves in cholinergic-hypertension & renal sodium retention.

METHODS AND RESULTS: Bilateral renal denervation (RND) and immune ablation of CD161a+ immune cells was performed in young prehypertensive SHR followed by infusion of either saline or nicotine (15mg/kg/day) for two weeks. Immune ablation was conducted by injection of unconjugated azide-free antibody targeting rat CD161a. Blood pressure was monitored by tail cuff plethysmography. Tissues were harvested at the end of infusion. Nicotine induced premature hypertension, renal expression of the sodium-potassium-chloride co-transporter (NKCC2), increases in renal sodium retention, and infiltration of CD161a+/CD68+ macrophages into the renal medulla of animals. All of these effects were abrogated or prevented by RND and ablation of CD161a+ immune cells.

CONCLUSIONS: Cholinergic activation of CD161a+ positive immune cells leads to the premature development of hypertension in SHR, at least partly, through increased renal expression of NKCC2 and renal sodium retention. Effects on chemotaxis of CD161a+ macrophages to the renal medulla, decreased renal expression of NKCC2, and renal sodium retention appear to play a part in the prevention of cholinergic hypertension as a result of RND. The CD161a+ immune cells are necessary and essential for this pro-hypertensive nicotine-mediated inflammatory response.

Link to journal online: https://www.physiology.org/doi/abs/10.1152/ajpheart.00234.2019

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