Increase in Bioavailability of Nitric Oxide After Renal Denervation Improves Kidney Function in Sheep With Hypertensive Kidney Disease
Open accessAbstract
Overactivity of renal sympathetic nerves and nitric oxide (NO) deficiency occur in hypertensive chronic kidney disease (CKD). In sheep with hypertensive CKD and NO deficiency, renal denervation (RDN) reduces blood pressure and improves kidney function (glomerular filtration rate). We hypothesized that this improvement in glomerular filtration rate after RDN is associated with increased NO bioavailability. In this study, glomerular filtration rate response to systemic inhibition of NOS (NO synthase) was examined in healthy and CKD sheep at 2 and 30 months after a sham (intact nerves) or RDN procedure. Basal urinary total nitrate (nitrate+nitrite) excretion was examined at 2 and 30 months, and kidney protein expression of endothelial and neuronal NOS was assessed at 30 months. Urinary nitrate+nitrite in CKD-RDN and healthy sheep was ≈50% to 70% greater than in CKD-intact. During NOS inhibition, the fall in glomerular filtration rate in CKD-RDN sheep was ≈20% greater than in CKD-intact. These effects in CKD-RDN sheep were similar to those in healthy sheep. Endothelial NOS protein expression was lower in CKD-intact sheep compared with healthy sheep and compared with CKD-RDN. In summary, RDN normalizes NO bioavailability and restores contribution of NO to renal hemodynamics in CKD. These changes may promote improvements in kidney function and sustained blood pressure lowering after RDN in hypertensive CKD.
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Preclinical studies in sheep and rat models show that renal denervation improves renal function and reduces blood pressure in chronic kidney disease, with effects beyond blood pressure reduction.
“However, the beneficial effects of RDN on CKD are not limited to its antihypertensive effects, with studies showing direct improvement in renal function following ablation of the renal nerves.”
From Renal nerves in physiology, pathophysiology and interoception (2025) · cites this paper as [110]
The Basal Cardiovascular and Renal Function results report lower blood pressure and, at 30 months, higher renal blood flow and glomerular filtration rate after denervation in sheep with CKD. The Discussion links improved renal hemodynamics to nitric oxide, supporting a renal effect beyond simply reporting blood-pressure reduction. This paper does not report a rat experiment showing improved renal function, nor does it establish that the kidney-function improvement is independent of blood-pressure lowering. (LLM, conf=0.82)
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- Authors
- Singh, R. R., McArdle, Z. M., Booth, L. C., May, C. N., Head, G. A., Moritz, K. M., Schlaich, M. P., & Denton, K. M.
- Affiliations
- Monash University (AU)
- The University of Melbourne (AU)
- Baker Heart and Diabetes Institute, Melbourne, Australia (G.A.H., M.P.S.)
- The University of Queensland (AU)
- Baker Heart and Diabetes Institute (AU)
- ORCID
- Venue
- Hypertension
- Published
- 2021-04
- Volume
- 77
- Issue
- 4
- Pages
- 1299-1310
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W3134306672
- Cited by
- 15
- References
- 44
- Citations by year
- 2026: 2 · 2025: 5 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 2
- FWCI
- 1.34
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- UWA Profiles and Research Repository (UWA) (submittedVersion)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Blood Pressure and Hypertension Studies
- Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Keywords
- renal denervation, nitric oxide bioavailability, glomerular filtration rate, nitric oxide synthase inhibition, endothelial nitric oxide synthase, neuronal nitric oxide synthase, renal hemodynamics, sheep model
- MeSH terms
- Animals, Blood Pressure, Hypertension, Renal, Kidney, Kidney Function Tests, Nephritis, Nitric Oxide, Sheep, Sympathectomy, Treatment Outcome
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