The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension
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 i...
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MDPI AG
2020-06-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/11/4041 |
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| author | Rocio Bautista-Pérez Oscar Pérez-Méndez Agustina Cano-Martínez Ursino Pacheco José Santamaría Fernando Rodríguez-Sámano Bernardo Rodríguez-Iturbe L. Gabriel Navar Martha Franco |
| author_facet | Rocio Bautista-Pérez Oscar Pérez-Méndez Agustina Cano-Martínez Ursino Pacheco José Santamaría Fernando Rodríguez-Sámano Bernardo Rodríguez-Iturbe L. Gabriel Navar Martha Franco |
| author_sort | Rocio Bautista-Pérez |
| collection | DOAJ |
| description | 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<sup>−1</sup> min<sup>−1</sup>, 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<sup>−5</sup>) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm<sup>−5</sup>) 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% (<i>p</i> < 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. |
| first_indexed | 2024-03-10T19:21:58Z |
| format | Article |
| id | doaj.art-946da371501845ce9fc4636fcf0e9f05 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T19:21:58Z |
| publishDate | 2020-06-01 |
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| spelling | doaj.art-946da371501845ce9fc4636fcf0e9f052023-11-20T02:56:23ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-06-012111404110.3390/ijms21114041The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced HypertensionRocio Bautista-Pérez0Oscar Pérez-Méndez1Agustina Cano-Martínez2Ursino Pacheco3José Santamaría4Fernando Rodríguez-Sámano5Bernardo Rodríguez-Iturbe6L. Gabriel Navar7Martha Franco8Department of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez”, México City 14080, MexicoDepartment of Molecular Biology, Instituto Nacional de Cardiología "Ignacio Chávez”, México City 14080, MexicoDepartment of Physiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, MexicoDepartment of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, MexicoDepartment of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, MexicoDepartment of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, MexicoDepartment of Nephrology, Instituto Nacional de Cardiología "Ignacio Chávez”, México City 14080, MexicoDepartment of Physiology and Hypertension and Renal Center, Tulane University School of Medicine New Orleans, New Orleans, LA 70112, USADepartment of Cardio-Renal Pathophysiology, Instituto Nacional de Cardiología “Ignacio Chávez”, México City 14080, MexicoPurinergic 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<sup>−1</sup> min<sup>−1</sup>, 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<sup>−5</sup>) and efferent (2.62 ± 0.03 to 1.29 ± 0.09 dyn.s.cm<sup>−5</sup>) 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% (<i>p</i> < 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.https://www.mdpi.com/1422-0067/21/11/4041purinergic receptorsP2X7 receptorsinflammationkidneyhypertensionangiotensin II |
| spellingShingle | Rocio Bautista-Pérez Oscar Pérez-Méndez Agustina Cano-Martínez Ursino Pacheco José Santamaría Fernando Rodríguez-Sámano Bernardo Rodríguez-Iturbe L. Gabriel Navar Martha Franco The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension International Journal of Molecular Sciences purinergic receptors P2X7 receptors inflammation kidney hypertension angiotensin II |
| title | The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension |
| title_full | The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension |
| title_fullStr | The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension |
| title_full_unstemmed | The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension |
| title_short | The Role of P2X7 Purinergic Receptors in the Renal Inflammation Associated with Angiotensin II-Induced Hypertension |
| title_sort | role of p2x7 purinergic receptors in the renal inflammation associated with angiotensin ii induced hypertension |
| topic | purinergic receptors P2X7 receptors inflammation kidney hypertension angiotensin II |
| url | https://www.mdpi.com/1422-0067/21/11/4041 |
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