Hypertension (Dallas, Tex. : 1979)
July 27, 2026 · via Europe PMC
Renal Denervation Modulates Hypothalamic Neuroinflammation via P2X7R/PI3K/Akt.
Liang W, Liu Q, Wang Q, +6 more, Yu J.
AI summary — for doctors, generated from the abstract only
In spontaneously hypertensive rats, renal denervation lowered blood pressure and dampened ATP/P2X7R/PI3K/Akt neuroinflammatory signaling in the hypothalamic paraventricular nucleus.
What was studied
Eight-week-old male spontaneously hypertensive rats were randomized to sham surgery or combined physical and chemical renal denervation (n = 8 per group), with longitudinal tail-cuff blood pressure, cardiac histology, and paraventricular nucleus ATP, P2X7R expression and PI3K/Akt phosphorylation measured, plus pharmacological validation with a selective P2X7R antagonist.
Key findings
- Renal denervation significantly reduced systolic blood pressure, from 210.3 to 143.2 mm Hg; the exact p value is not fully captured in the abstract.
- Further results on ATP levels, P2X7R expression, PI3K/Akt phosphorylation, cardiac injury and the P2X7R antagonist experiments are truncated; specific statistics not fully captured in the abstract.
- The authors concluded that denervation attenuated central ATP-related neuroinflammatory signaling beyond peripheral sympathetic disruption.
- They propose the ATP/P2X7R/PI3K/Akt axis as a candidate pathway linking renal signaling to central sympathetic regulation.
Clinical relevance
This is a small preclinical rat study offering a candidate central mechanism for an intervention already used in resistant hypertension, and it does not speak to patient selection or outcomes.
Who should care
Limitations
Only eight animals per group of a single sex and strain were studied, much of the results section is truncated in the abstract, and genetic rat hypertension differs from human disease.
Renal denervation may work partly through calming inflammatory signaling in the brain, a mechanism so far shown only in rats.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Background
Hypertension remains the leading global contributor to cardiovascular mortality. Although renal denervation (RDN) has demonstrated efficacy, the central neurobiological mechanisms sustaining its sympathoinhibitory effects remain unclear. We investigated whether RDN modulates the ATP and P2X7R (P2X7 receptor)/PI3K (phosphoinositide 3-kinase)/Akt (protein kinase B) signaling axis in the hypothalamic paraventricular nucleus to attenuate neuroinflammation and blood pressure.
Methods
Eight-week-old male spontaneously hypertensive rats were randomly assigned to either sham surgery or RDN (combined physical/chemical ablation; n=8 per group). Systolic blood pressure was longitudinally monitored using tail-cuff plethysmography. Cardiac target-organ injury was assessed using hematoxylin-eosin and Masson's trichrome staining. ATP levels, P2X7R expression, and PI3K/Akt phosphorylation in the paraventricular nucleus were quantified by ELISA, Western blotting, and immunofluorescence. A selective P2X7R antagonist (HY-50697/A-740003) was used for pharmacological validation.
Results
RDN significantly reduced systolic blood pressure in spontaneously hypertensive rats (from 210.3 to 143.2 mm Hg, PP<0.0001), downregulated P2X7R protein expression, and suppressed pathological activation of the PI3K/Akt signaling pathway, accompanied by reduced proinflammatory cytokine production. Pharmacological inhibition of P2X7R functionally phenocopied the antihypertensive and central anti-inflammatory effects induced by RDN.
Conclusions
RDN was associated with reduced blood pressure and attenuation of central ATP-related neuroinflammatory signaling, beyond peripheral sympathetic disruption. The ATP/P2X7R/PI3K/Akt axis may represent a candidate pathway linking renal signaling to central sympathetic regulation, warranting further investigation as a potential mechanistic target in resistant hypertension.
DOI
10.1161/hypertensionaha.126.26793
PMID
42504620
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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