Renal Inflammation in DOCA-Salt Hypertension: Role of Renal Nerves and Arterial Pressure
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Recent reports indicate that, in addition to treating hypertension, renal denervation (RDN) also mitigates renal inflammation. However, because RDN decreases renal perfusion pressure, it is unclear whether these effects are because of the direct effects of RDN on inflammatory signaling or secondary to decreased arterial pressure (AP). Therefore, this study was conducted to elucidate the contribution of renal nerves to renal inflammation in the deoxycorticosterone (DOCA)-salt rat, a model in which RDN decreases AP and abolishes renal inflammation. In Experiment 1, we assessed the temporal changes in renal inflammation by measuring renal cytokines and AP in DOCA-salt rats. Uninephrectomized (1K) adult male Sprague Dawley rats that received surgical RDN or sham (Sham) were administered DOCA (100 mg, SC) and 0.9% saline for 21 days. AP was measured by radiotelemetry, and urinary cytokine excretion was measured repeatedly. In Experiment 2, the contribution of renal nerves in renal inflammation was assessed in a 2-kidney DOCA-salt rat to control for renal perfusion pressure. DOCA-salt treatment was administered after unilateral (U-)RDN. In Experiment 1, DOCA-salt–induced increases in AP and renal inflammation (assessed by urinary cytokines) were attenuated by RDN versus Sham. In Experiment 2, GRO/KC (growth-related oncogene/keratinocyte chemoattractant), MCP (monocyte chemoattractant protein)-1, and macrophage infiltration were lower in the denervated kidney versus the contralateral Sham kidney. No differences in T-cell infiltration were observed. Together, these data support the hypothesis that renal nerves mediate, in part, the development of renal inflammation in the DOCA-salt rat independent of hypertension. The mechanisms and cell-specificity mediating these effects require further investigation.
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Elevated pro-inflammatory cytokines are found in renal parenchyma and urine of rodent hypertension models, including IL-1β, IL-2 and MCP1 in DOCA-salt rats and mice and in 2K1C rats.
“Our laboratory and others identified elevated levels of pro-inflammatory cytokines in the renal parenchyma and urine of rodent models of hypertension20,83, including elevations in IL-1β, IL-2 and MCP1 in the DOCA-salt rat73 and mouse84 and in the 2K1C rat20.”
From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [73]
Multiple preclinical studies show that total renal denervation causes a significant and sustained fall in mean arterial blood pressure.
“Multiple preclinical studies have demonstrated that total RDN (TRDN, defined as ablation of the sympathetic efferent and sensory afferent nerves) causes a significant and sustained reduction in mean arterial blood pressure20,69–73.”
From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [73]
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References 52 · Cited by 58
- Authors
- Banek, C. T., Gauthier, M. M., Van Helden, D. A., Fink, G. D., & Osborn, J. W.
- Affiliations
- University of Minnesota (US)
- From the Department of Integrative Biology and Physiology, University of Minnesota, Minneapolis (C.T.B., M.M.G., D.A.V.H., J.W.O.)
- Michigan State University (US)
- Corresponding author
- Osborn, John W.
- Venue
- Hypertension
- Published
- 2019-05
- Volume
- 73
- Issue
- 5
- Pages
- 1079-1086
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC6540804
- OpenAlex
- W2921282191
- Cited by
- 58
- References
- 52
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 9 · 2019: 1
- FWCI
- 5.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (K99HL141650, R01HL116476, R00HL141650)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Hormonal Regulation and Hypertension
- Keywords
- renal inflammation, renal denervation, DOCA-salt hypertension, renal nerves, urinary cytokines, MCP-1, macrophage infiltration, T cell infiltration, renal perfusion pressure, unilateral nephrectomy
- MeSH terms
- Animals, Blood Pressure, Disease Models, Animal, Hypertension, Kidney, Male, Nephritis, Sympathetic Nervous System, Cytokines, Rats, Sprague-Dawley, Sodium Chloride, Dietary, Rats, Desoxycorticosterone Acetate
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