The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension
Open accessAbstract
Purinergic receptors play a central role in the renal pathophysiology of angiotensin II-induced hypertension, since elevated ATP chronically activates P2X7 receptors in this model. The changes induced by the P2X antagonist Brilliant blue G (BBG) in glomerular hemodynamics and in tubulointerstitial inflammation resulting from angiotensin II infusion were studied. Rats received angiotensin II (435 ng kg−1 min−1, 2 weeks) alone or in combination with BBG (50 mg/kg/day intraperitoneally). BBG did not modify hypertension (214.5 ± 1.4 vs. 212.7 ± 0.5 mmHg), but restored to near normal values afferent (7.03 ± 1.00 to 2.97 ± 0.27 dyn.s.cm−5) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm−5) arteriolar resistances, glomerular plasma flow (79.23 ± 3.15 to 134.30 ± 1.11 nL/min), ultrafiltration coefficient (0.020 ± 0.002 to 0.036 ± 0.003 nL/min/mmHg) and single nephron glomerular filtration rate (22.28 ± 2.04 to 34.46 ± 1.54 nL/min). Angiotensin II induced overexpression of P2X7 receptors in renal tubular cells and in infiltrating T and B lymphocytes and macrophages. All inflammatory cells were increased by angiotensin II infusion and reduced by 20% to 50% (p < 0.05) by BBG administration. Increased IL-2, IL-6, TNFα, IL-1β, IL-18 and overexpression of NLRP3 inflammasome were induced by angiotensin II and suppressed by BBG. These studies suggest that P2X7 receptor-mediated renal vasoconstriction, tubulointerstitial inflammation and activation of NLRP3 inflammasome are associated with angiotensin II-induced hypertension.
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P2X7 receptor blockade prevents Ang II-triggered pro-inflammatory responses.
“Indeed, evidence demonstrates that P2X7 receptor blockade prevents Ang II-triggered pro-inflammatory responses [119].”
From Hyperactivation of P2X7 receptors as a culprit of COVID-19 neuropathology (2021) · cites this paper as [119]
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References 49 · Cited by 25
Research works printed but not linked: 1
- [36]Volker V. Unwin R. Inscho E.W. Leipziger J. Kishore B.K. Role of extracellular nucleotides in renal function Physiol Rev. 2020 100 211 269 31437091 PMC6985785
- Authors
- Bautista-Pérez, R., Pérez-Méndez, O., Cano-Martínez, A., Pacheco, U., Santamaría, J., Rodríguez-Sámano, F., Rodríguez-Iturbe, B., Navar, L. G., & Franco, M.
- Affiliations
- Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez”, México City 14080, Mexico
- Instituto Nacional de Cardiología (MX)
- Department of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, Mexico
- Department of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez”, México City 14080, Mexico
- Tulane University (US)
- Corresponding author
- Franco, Martha
- Venue
- International Journal of Molecular Sciences
- Publisher
- MDPI AG
- Published
- 2020-06-05
- Volume
- 21
- Issue
- 11
- Pages
- 4041
- ISSN
- 1422-0067 (ISSN-L)
- PMC
- PMC7312644
- OpenAlex
- W3032971364
- Cited by
- 25
- References
- 49
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 4 · 2022: 7 · 2021: 2 · 2020: 3
- FWCI
- 2.51
- Type
- journal article
- Language
- en
- Open access
- gold
- dx.doi.org
- Licence
- Locations
- International Journal of Molecular Sciences (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institute of General Medical Sciences (P30-GM-103337)
- National Council of Sciences and Technology (CONACYT) Mexico (219981)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Health Sciences › Medicine › Nephrology › Gout, Hyperuricemia, Uric Acid
- Keywords
- P2X7 receptor, purinergic receptors, angiotensin II-induced hypertension, renal inflammation, Brilliant Blue G, tubulointerstitial inflammation, glomerular hemodynamics, NLRP3 inflammasome, cytokines, renal vasoconstriction, macrophages, lymphocytes
- MeSH terms
- Angiotensin II, Animals, Biopsy, Disease Susceptibility, Hypertension, Immunity, Nephritis, Proteinuria, Punctures, Cytokines, Disease Management, Rats, Receptors, Purinergic P2X7, Arterial Pressure
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