# Resistance exercise exerts anti-hypertensive effects and downregulates NTPDase/CD39 and ecto-5′-nucleotidase/CD73 expression in patients with chronic kidney disease undergoing hemodialysis

**Authors:** Angela Makeli Kososki Dalagnol, Francini Franscescon, Matheus Chimelo Bianchini, Josiano Guilherme Puhle, Keroli Eloiza Tessaro da Silva, Helamã Moraes Santos, Sarah Franco Vieira de Oliveira Maciel, Débora Tavares de Resende e Silva

PMC · DOI: 10.1007/s11302-025-10121-7 · 2026-01-21

## TL;DR

Resistance exercise lowers blood pressure and reduces enzyme activity linked to purinergic signaling in CKD patients on hemodialysis.

## Contribution

This study shows resistance exercise mitigates purinergic signaling and has anti-hypertensive effects in CKD patients.

## Key findings

- Resistance exercise significantly reduced systolic blood pressure in CKD patients.
- NTPDase/CD39 and ecto-5′-nucleotidase/CD73 expression were downregulated after resistance exercise.
- Extracellular ATP levels were restored in CKD patients following resistance exercise.

## Abstract

Chronic kidney disease (CKD) affects approximately 13.4% of the global population and significantly impacts patients’ quality of life. This study aimed to investigate the effects of resistance exercise on blood pressure and purinergic signaling in patients with CKD. Here, 28 patients with CKD performed a 12-week resistance exercise protocol during hemodialysis. Blood samples were collected before and after the intervention. Biochemical analyses, for example, NTPDases, ecto-5′-nucleotidase, and adenosine deaminase, were measured in platelets. Flow cytometry was performed to investigate CD39 and CD73 expression on lymphocytes. In addition, extracellular ATP and blood pressure were analyzed. Our findings revealed that patients with CKD present high systolic blood pressure (p = 0.0002) compared to control, and resistance exercise reduces blood pressure in these patients (p = 0.007). Regarding purinergic signaling, an increase in NTPDases, ecto-5′-nucleotidase, and adenosine deaminase was observed in patients with CKD (p = 0.0001; p = 0.0001; p = 0.0001; p = 0.0007, respectively). Surprisingly, after resistance exercise, NTPDase/ATP and ecto-5′-nucleotidase decreased (p = 0.0006; p = 0.02). CD39 and CD73 expression significantly increased on lymphocytes of CKD patients compared to control (p = 0.004; p = 0.0002, respectively). After resistance exercise, CD39 and CD73 expression was downregulated. Extracellular ATP levels were decreased in CKD (p = 0.0001), and resistance exercise restored these levels. In conclusion, CKD patients present high activity and expression of CD39 and CD73 enzymes, and resistance exercise mitigated purinergic exacerbation and presents anti-hypertensive effects in patients with CKD.

The online version contains supplementary material available at 10.1007/s11302-025-10121-7.

## Linked entities

- **Proteins:** ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1), NT5E (5'-nucleotidase ecto)
- **Diseases:** chronic kidney disease (MONDO:0005300)

## Full-text entities

- **Genes:** GH1 (growth hormone 1) [NCBI Gene 2688] {aka GH, GH-N, GHB5, GHN, IGHD1A, IGHD1B}, P2RY1 (purinergic receptor P2Y1) [NCBI Gene 5028] {aka P2Y1, SARCC}, CD4 (CD4 molecule) [NCBI Gene 920] {aka CD4mut, IMD79, Leu-3, OKT4D, T4}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, CD8A (CD8 subunit alpha) [NCBI Gene 925] {aka CD8, CD8alpha, IMD116, Leu2, p32}, INS (insulin) [NCBI Gene 3630] {aka IDDM, IDDM1, IDDM2, ILPR, IRDN, MODY10}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, P2RY12 (purinergic receptor P2Y12) [NCBI Gene 64805] {aka ADPG-R, BDPLT8, HORK3, P2T(AC), P2Y(12)R, P2Y(AC)}, IL4 (interleukin 4) [NCBI Gene 3565] {aka BCGF-1, BCGF1, BSF-1, BSF1, IL-4}, GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], AGT (angiotensinogen) [NCBI Gene 183] {aka ANHU, SERPINA8, hFLT1}, APC (APC regulator of Wnt signaling pathway) [NCBI Gene 324] {aka BTPS2, DESMD, DP2, DP2.5, DP3, GS}, REN (renin) [NCBI Gene 5972] {aka ADTKD4, HNFJ2, RTD}, ADA (adenosine deaminase) [NCBI Gene 100] {aka ADA1}, FNDC5 (fibronectin type III domain containing 5) [NCBI Gene 252995] {aka FRCP2, irisin}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, ENTPD1 (ectonucleoside triphosphate diphosphohydrolase 1) [NCBI Gene 953] {aka ATP-DPH, ATPDase, CD39, NTPDase-1, SPG64}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, NT5E (5'-nucleotidase ecto) [NCBI Gene 4907] {aka CALJA, CD73, E5NT, NT, NT5, NTE}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, MSTN (myostatin) [NCBI Gene 2660] {aka GDF8, MSLHP}, EPO (erythropoietin) [NCBI Gene 2056] {aka DBAL, ECYT5, EP, MVCD2}
- **Diseases:** diabetes (MESH:D003920), insulin dependents (MESH:D003922), hip medial rotation (MESH:D025981), depression (MESH:D003866), arteriovenous fistula (MESH:D001164), mineral and bone disorder (MESH:D012080), polycystic kidney disease (MESH:D007690), Atherosclerosis (MESH:D050197), Cardiovascular disease (MESH:D002318), death (MESH:D003643), nephrotoxic injury (MESH:D014947), hypothyroidism (MESH:D007037), DM type II (MESH:D009223), arterial hypertension (MESH:D000081029), muscle hypertrophy (MESH:C536106), endothelial dysfunction (MESH:D014652), left ventricular hypertrophy (MESH:D017379), platelet aggregation (MESH:D001791), CKD (MESH:D051436), hypertrophy (MESH:D006984), acute myocardial infarction (MESH:D009203), dyslipidemia (MESH:D050171), kidney disease (MESH:D007674), chronic inflammation (MESH:D007249), vascular calcification (MESH:D061205), autoimmune diseases (MESH:D001327), hyperthyroidism (MESH:D006980), tissue damage (MESH:D017695), stroke (MESH:D020521), anemia (MESH:D000740), Sarcopenia (MESH:D055948), uremic (MESH:D006463), kidney failure (MESH:D051437), nephritis (MESH:D009393), hypertension (MESH:D006973), cancer (MESH:D009369), medial (MESH:D020423), reduced systolic blood pressure (MESH:D007022), muscle loss (MESH:D009135)
- **Chemicals:** CaCl2 (MESH:D002122), ammonium chloride (MESH:D000643), EDTA (MESH:D004492), simvastatin (MESH:D019821), inorganic phosphate (MESH:D010710), Lymphoprep (MESH:C038920), AMP (MESH:D000249), Coomassie blue (MESH:C048139), ATP (MESH:D000255), aldosterone (MESH:D000450), phenol (MESH:D019800), nucleotide (MESH:D009711), NaCl (MESH:D012965), H2O (MESH:D014867), KCl (MESH:D011189), norepinephrine (MESH:D009638), alcohol (MESH:D000438), HEPES (MESH:D006531), ADP (MESH:D000244), NaOH (MESH:D012972), calcium (MESH:D002118), TCA (MESH:D014238), lipid (MESH:D008055), Pi (MESH:D010716), Ficoll (MESH:D005362), sodium nitroprusside (MESH:D009599), glucose (MESH:D005947), Adenosine (MESH:D000241), creatinine (MESH:D003404), levothyroxine (MESH:D013974), TXB2 (MESH:D013929), Ca2+ (-), NO (MESH:D009569), ammonia (MESH:D000641)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12824041/full.md

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Source: https://tomesphere.com/paper/PMC12824041