The authors enrolled 57 patients who underwent Roux-en-Y gastric bypass (RYGB) at a single center between December 2010 and May 2025. Patients were classified as normotensive (n = 24) or hypertensive (n = 33) according to diagnostic criteria for hypertension. Baseline and postoperative clinical data were collected. Daily sodium intake was estimated from 24‑hour urinary sodium excretion; the median preoperative sodium intake for the cohort was 10.45 (8.19, 15.58) g/day.
After RYGB, both systolic and diastolic blood pressure values decreased compared with baseline: mean systolic BP fell from 133.26 ± 16.48 mmHg to 118.23 ± 15.40 mmHg, and mean diastolic BP fell from 83.16 ± 12.44 mmHg to 74.54 ± 8.80 mmHg (both P < 0.05). A positive correlation was observed between preoperative sodium intake and the magnitude of postoperative systolic BP reduction (R = 0.326, P = 0.013), indicating larger BP decreases in patients with higher baseline sodium consumption.
Forty‑eight male 6‑week‑old Dahl salt‑sensitive rats were fed an 8% high‑salt diet for 8 weeks to induce salt‑sensitive hypertension. Thirty modeled rats were randomized to RYGB (n = 15) or sham operation (n = 15). The remaining 18 rats were allocated to control (saline, n = 6), liraglutide (0.2 mg·kg‑1·d‑1, n = 6) and liraglutide + EX9‑39 (liraglutide plus GLP‑1R antagonist EX9‑39 at 75 μg·kg‑1·d‑1, n = 6).
At 8 weeks after surgery, RYGB rats had significantly lower blood pressure than sham rats by both non‑invasive tail‑cuff and invasive radiotelemetry measures. Tail‑cuff systolic BP in the RYGB group was 125.33 ± 12.16 mmHg versus 182.00 ± 11.61 mmHg in sham. Twenty‑four‑hour mean systolic BP and diastolic BP were similarly reduced in the RYGB group compared with sham (all P < 0.05).
Compared with sham surgery, RYGB reduced the ratio of vascular wall thickness to outer vessel diameter and increased endothelium‑dependent vasodilation of mesenteric arteries. RYGB rats exhibited less glomerular collagen deposition on histologic staining. Measures of renal function—serum creatinine, blood urea nitrogen (BUN), and urinary protein—were lower in RYGB animals compared with sham (all P < 0.05). Inflammatory markers tumor necrosis factor‑α and interleukin‑6 were reduced in renal cortex of RYGB rats versus sham.
Biochemically, RYGB increased circulating GLP-1 levels and upregulated renal cortical GLP‑1 receptor expression. Concurrently, serum AngⅡ and renal cortical expression of ACE1 and AGTR1 were decreased in RYGB rats compared with sham (all P < 0.05). The phosphorylation level of the renal Na+/H+ exchanger NHE3 (phospho‑NHE3) and total NHE3 were assessed; the RYGB group showed higher NHE3 phosphorylation compared with sham.
These molecular changes are presented by the authors as evidence that RYGB modifies the renal renin‑angiotensin system (RAS) and NHE3 activity in a GLP‑1–dependent manner.
In the pharmacologic arms, liraglutide treatment lowered tail‑cuff systolic BP compared with control (167.00 ± 9.98 mmHg vs. 182.00 ± 6.26 mmHg, P < 0.05). The abstract indicates that some liraglutide effects were attenuated by co‑administration of the GLP‑1 receptor antagonist EX9‑39, consistent with a GLP‑1R–mediated mechanism; specific additional comparative numeric results and statistical details for these groups were reported in the source.
In vitro studies used rat renal epithelial NRK‑52E cells with four groups: high‑salt (160 mmol/L NaCl), high‑salt + liraglutide (100 nmol/L), high‑salt + liraglutide + EX9‑39 (100 nmol/L liraglutide + 150 nmol/L EX9‑39), and vehicle control. Western blotting assessed ACE1, AGTR1, phosphorylated NHE3 and total NHE3.
High salt induced increases in ACE1, AGTR1 and phosphorylated NHE3. Liraglutide modulated these protein expression changes, and the addition of EX9‑39 reversed liraglutide’s effects, supporting a role for GLP-1R signaling in regulating RAS components and NHE3 phosphorylation under high‑salt conditions.
Across clinical, animal, and cellular experiments the investigators report that RYGB reduces salt‑sensitive blood pressure and improves vascular and renal structure and function. The data link increased circulating GLP-1 and enhanced renal GLP‑1R expression after RYGB with downregulation of the RAS (lower AngⅡ, ACE1, AGTR1) and modulation of NHE3 phosphorylation. Pharmacologic mimicry with liraglutide and attenuation by EX9‑39 support a GLP-1–mediated inhibition of the RAS/NHE3 axis as a contributory mechanism for improved salt‑sensitive hypertension after RYGB.
The article is published in Chinese; the abstract and reported findings above summarize the data presented. Any additional methodological specifics, extended numerical results, long‑term follow‑up data, or subgroup analyses not included in the source abstract were not reported here.