Kidney Res Clin Pract.
2019 Mar;38(1):6-14. 10.23876/j.krcp.18.0143.
Renal sympathetic nerve activation via α₂-adrenergic receptors in chronic kidney disease progression
- Affiliations
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- 1Department of Cellular and Integrative Physiology, University of Nebraska Medical Center, Omaha, NE, USA. bpadanilam@unmc.edu
- 2Department of Anatomy, Jeju National University School of Medicine, Jeju, Korea.
- 3Department of Biomedicine and Drug Development, Jeju National University, Jeju, Korea.
- 4Department of Internal Medicine, Section of Nephrology, University of Nebraska Medical Center, Omaha, NE, USA.
- KMID: 2447139
- DOI: http://doi.org/10.23876/j.krcp.18.0143
Abstract
- Chronic kidney disease (CKD) is increasing worldwide without an effective therapeutic strategy. Sympathetic nerve activation is implicated in CKD progression, as well as cardiovascular dysfunction. Renal denervation is beneficial for controlling blood pressure (BP) and improving renal function through reduction of sympathetic nerve activity in patients with resistant hypertension and CKD. Sympathetic neurotransmitter norepinephrine (NE) via adrenergic receptor (AR) signaling has been implicated in tissue homeostasis and various disease progressions, including CKD. Increased plasma NE level is a predictor of survival and the incidence of cardiovascular events in patients with end-stage renal disease, as well as future renal injury in subjects with normal BP and renal function. Our recent data demonstrate that NE derived from renal nerves causes renal inflammation and fibrosis progression through alpha-2 adrenergic receptors (α₂-AR) in renal fibrosis models independent of BP. Sympathetic nerve activation-associated molecular mechanisms and signals seem to be critical for the development and progression of CKD, but the exact role of sympathetic nerve activation in CKD progression remains undefined. This review explores the current knowledge of NE-α₂-AR signaling in renal diseases and offers prospective views on developing therapeutic strategies targeting NE-AR signaling in CKD progression.
Keyword
MeSH Terms
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Blood Pressure
Denervation
Disease Progression
Fibrosis
Homeostasis
Humans
Hypertension
Incidence
Inflammation
Kidney Failure, Chronic
Neurotransmitter Agents
Norepinephrine
Plasma
Prospective Studies
Receptors, Adrenergic
Receptors, Adrenergic, alpha-2
Renal Insufficiency, Chronic*
Reperfusion Injury
Neurotransmitter Agents
Norepinephrine
Receptors, Adrenergic
Receptors, Adrenergic, alpha-2
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