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Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb

Sodium transport in the thick ascending loop of Henle (TAL) is tightly regulated by numerous factors, especially angiotensin II (Ang II), a key end‐product of the renin‐angiotensin system (RAS). However, an alternative end‐product of the RAS, angiotensin‐(1‐7) [Ang‐(1‐7)], may counter some of the An...

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Autores principales: Dibo, Paula, Marañón, Rodrigo O., Chandrashekar, Kiran, Mazzuferi, Fernando, Silva, Guillermo B., Juncos, Luis A., Juncos, Luis I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401662/
https://www.ncbi.nlm.nih.gov/pubmed/30839176
http://dx.doi.org/10.14814/phy2.14015
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author Dibo, Paula
Marañón, Rodrigo O.
Chandrashekar, Kiran
Mazzuferi, Fernando
Silva, Guillermo B.
Juncos, Luis A.
Juncos, Luis I.
author_facet Dibo, Paula
Marañón, Rodrigo O.
Chandrashekar, Kiran
Mazzuferi, Fernando
Silva, Guillermo B.
Juncos, Luis A.
Juncos, Luis I.
author_sort Dibo, Paula
collection PubMed
description Sodium transport in the thick ascending loop of Henle (TAL) is tightly regulated by numerous factors, especially angiotensin II (Ang II), a key end‐product of the renin‐angiotensin system (RAS). However, an alternative end‐product of the RAS, angiotensin‐(1‐7) [Ang‐(1‐7)], may counter some of the Ang II actions. Indeed, it causes vasodilation and promotes natriuresis through its effects in the proximal and distal tubule. However, its effects on the TAL are unknown. Because the TAL expresses the Mas receptor, an Ang‐(1‐7) ligand, which in turn may increase NO and inhibit Na+ transport, we hypothesized that Ang‐(1‐7) inhibits Na transport in the TAL, via a Mas receptor/NO‐dependent mechanism. We tested this by measuring transport‐dependent oxygen consumption (VO (2)) in TAL suspensions. Administering Ang‐(1‐7) decreased VO (2); an effect prevented by dimethyl amiloride and furosemide, signifying that Ang‐(1‐7) inhibits transport‐dependent VO (2) in TAL. Ang‐(1‐7) also increased NO levels, known inhibitors of Na+ transport in the TAL. The effects of Ang‐(1‐7) on VO (2), as well as on NO levels, were ameliorated by the Mas receptor antagonist, D‐Ala, in effect suggesting that Ang‐(1‐7) may inhibit transport‐dependent VO (2) in TAL via Mas receptor‐dependent activation of the NO pathway. Indeed, blocking NO synthesis with L‐NAME prevented the inhibitory actions of Ang‐(1‐7) on VO (2). Our data suggest that Ang‐(1‐7) may modulate TAL Na+ transport via Mas receptor‐dependent increases in NO leading to the inhibition of transport activity.
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spelling pubmed-64016622019-03-18 Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb Dibo, Paula Marañón, Rodrigo O. Chandrashekar, Kiran Mazzuferi, Fernando Silva, Guillermo B. Juncos, Luis A. Juncos, Luis I. Physiol Rep Original Research Sodium transport in the thick ascending loop of Henle (TAL) is tightly regulated by numerous factors, especially angiotensin II (Ang II), a key end‐product of the renin‐angiotensin system (RAS). However, an alternative end‐product of the RAS, angiotensin‐(1‐7) [Ang‐(1‐7)], may counter some of the Ang II actions. Indeed, it causes vasodilation and promotes natriuresis through its effects in the proximal and distal tubule. However, its effects on the TAL are unknown. Because the TAL expresses the Mas receptor, an Ang‐(1‐7) ligand, which in turn may increase NO and inhibit Na+ transport, we hypothesized that Ang‐(1‐7) inhibits Na transport in the TAL, via a Mas receptor/NO‐dependent mechanism. We tested this by measuring transport‐dependent oxygen consumption (VO (2)) in TAL suspensions. Administering Ang‐(1‐7) decreased VO (2); an effect prevented by dimethyl amiloride and furosemide, signifying that Ang‐(1‐7) inhibits transport‐dependent VO (2) in TAL. Ang‐(1‐7) also increased NO levels, known inhibitors of Na+ transport in the TAL. The effects of Ang‐(1‐7) on VO (2), as well as on NO levels, were ameliorated by the Mas receptor antagonist, D‐Ala, in effect suggesting that Ang‐(1‐7) may inhibit transport‐dependent VO (2) in TAL via Mas receptor‐dependent activation of the NO pathway. Indeed, blocking NO synthesis with L‐NAME prevented the inhibitory actions of Ang‐(1‐7) on VO (2). Our data suggest that Ang‐(1‐7) may modulate TAL Na+ transport via Mas receptor‐dependent increases in NO leading to the inhibition of transport activity. John Wiley and Sons Inc. 2019-03-06 /pmc/articles/PMC6401662/ /pubmed/30839176 http://dx.doi.org/10.14814/phy2.14015 Text en © 2019 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of The Physiological Society and the American Physiological Society. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Research
Dibo, Paula
Marañón, Rodrigo O.
Chandrashekar, Kiran
Mazzuferi, Fernando
Silva, Guillermo B.
Juncos, Luis A.
Juncos, Luis I.
Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title_full Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title_fullStr Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title_full_unstemmed Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title_short Angiotensin‐(1‐7) inhibits sodium transport via Mas receptor by increasing nitric oxide production in thick ascending limb
title_sort angiotensin‐(1‐7) inhibits sodium transport via mas receptor by increasing nitric oxide production in thick ascending limb
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6401662/
https://www.ncbi.nlm.nih.gov/pubmed/30839176
http://dx.doi.org/10.14814/phy2.14015
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