Specific Afferent Renal Denervation Prevents Reduction in Neuronal Nitric Oxide Synthase Within the Paraventricular Nucleus in Rats With Chronic Heart Failure
Open accessAbstract
Renal denervation (RDN) has been shown to restore endogenous neuronal nitric oxide synthase (nNOS) in the paraventricular nucleus (PVN) and reduce sympathetic drive during chronic heart failure (CHF). The purpose of the present study was to assess the contribution of afferent renal nerves to the nNOS-mediated sympathetic outflow within the PVN in rats with CHF. CHF was induced in rats by ligation of the left coronary artery. Four weeks after surgery, selective afferent RDN (A-RDN) was performed by bilateral perivascular application of capsaicin on the renal arteries. Seven days after intervention, nNOS protein expression, nNOS immunostaining signaling, and diaphorase-positive stained cells were significantly decreased in the PVN of CHF rats, changes that were reversed by A-RDN. A-RDN reduced basal lumbar sympathetic nerve activity in rats with CHF (8.5%±0.5% versus 17.0%±1.2% of max). Microinjection of nNOS inhibitor L-NMMA (L-N G-monomethyl arginine citrate) into the PVN produced a blunted increase in lumbar sympathetic nerve activity in rats with CHF. This response was significantly improved after A-RDN (Δ lumbar sympathetic nerve activity: 25.7%±2.4% versus 11.2%±0.9%). Resting afferent renal nerves activity was substantially increased in CHF compared with sham rats (56.3%±2.4% versus 33.0%±4.7%). These results suggest that intact afferent renal nerves contribute to the reduction of nNOS in the PVN. A-RDN restores nNOS and thus attenuates the sympathoexcitation. Also, resting afferent renal nerves activity is elevated in CHF rats, which may highlight a crucial neural mechanism arising from the kidney in the maintenance of enhanced sympathetic drive in CHF.
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In a rat model of chronic heart failure, afferent renal denervation caused significant reductions in serum noradrenaline levels and normalized lumbar sympathetic nerve activity.
“Notably, in a rat model of chronic heart failure, ARDN caused significant reductions in serum noradrenaline levels and normalized lumbar sympathetic nerve activity6.”
From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [6]
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Neural afferents as potential targets to ameliorate FGF21-mediated sympathoexcitation
Katsurada, K., & Kario, K. (2021) · Hypertension Research · doi:10.1038/s41440-021-00811-1 · Cited by 1 · see citing works
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Renal Denervation for Treating Refractory Hypertension
Katsurada, K., & Kario, K. (2024) · Nihon Naika Gakkai Zasshi · doi:10.2169/naika.113.703
Self-citationProteinuria and renal function in hypertension: a role for the renal nerves
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- Authors
- Zheng, H., Katsurada, K., Liu, X., Knuepfer, M. M., & Patel, K. P.
- Affiliations
- University of South Dakota (US)
- University of Nebraska Medical Center (US)
- Saint Louis University (US)
- Nebraska Medical Center (US)
- Corresponding author
- Patel, Kaushik P.
- Venue
- Hypertension
- Published
- 2018-09
- Volume
- 72
- Issue
- 3
- Pages
- 667-675
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC6202134
- OpenAlex
- W2883892986
- Cited by
- 46
- References
- 58
- Citations by year
- 2026: 1 · 2025: 8 · 2024: 6 · 2023: 5 · 2022: 8 · 2021: 6 · 2020: 9 · 2019: 2 · 2018: 1
- FWCI
- 3.40
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (1r56hl124104-01, HL‐62222)
- National Heart, Lung, and Blood Institute (R56-HL-124104, R01 HL124104, P01HL062222)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK114663)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Keywords
- neuronal nitric oxide synthase, paraventricular nucleus, chronic heart failure, sympathetic activity, capsaicin, L-NMMA, renal afferent nerves, sympathoexcitation, coronary artery ligation, neurogenic inflammation
- MeSH terms
- Afferent Pathways, Animals, Capsaicin, Chronic Disease, Denervation, Enzyme Inhibitors, Heart Failure, Kidney, Male, Paraventricular Hypothalamic Nucleus, Sympathetic Nervous System, Rats, Sprague-Dawley, Sensory System Agents, omega-N-Methylarginine, Nitric Oxide Synthase Type I
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