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l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex

Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobio...

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Detalles Bibliográficos
Autores principales: Heikal, Lamia, Starr, Anna, Hussein, Dania, Prieto-Lloret, Jesus, Aaronson, Phil, Dailey, Lea Ann, Nandi, Manasi
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018612/
https://www.ncbi.nlm.nih.gov/pubmed/29963647
http://dx.doi.org/10.1016/j.jacbts.2018.01.015
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author Heikal, Lamia
Starr, Anna
Hussein, Dania
Prieto-Lloret, Jesus
Aaronson, Phil
Dailey, Lea Ann
Nandi, Manasi
author_facet Heikal, Lamia
Starr, Anna
Hussein, Dania
Prieto-Lloret, Jesus
Aaronson, Phil
Dailey, Lea Ann
Nandi, Manasi
author_sort Heikal, Lamia
collection PubMed
description Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH(4). Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction.
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spelling pubmed-60186122018-06-28 l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex Heikal, Lamia Starr, Anna Hussein, Dania Prieto-Lloret, Jesus Aaronson, Phil Dailey, Lea Ann Nandi, Manasi JACC Basic Transl Sci PRECLINICAL RESEARCH Reduced nitric oxide (NO) bioavailability correlates with impaired cardiovascular function. NO is extremely labile and has been challenging to develop as a therapeutic agent. However, NO bioavailability could be enhanced by pharmacologically targeting endogenous NO regulatory pathways. Tetrahydrobiopterin, an essential cofactor for NO production, is synthesized by GTP cyclohydrolase-1 (GCH1), which complexes with GCH1 feedback regulatory protein (GFRP). The dietary amino acid l-phenylalanine activates this complex, elevating vascular BH(4). Here, the authors demonstrate that l-phenylalanine administration restores vascular function in a rodent model of hypertension, suggesting the GCH1-GFRP complex represents a rational therapeutic target for diseases underpinned by endothelial dysfunction. Elsevier 2018-05-30 /pmc/articles/PMC6018612/ /pubmed/29963647 http://dx.doi.org/10.1016/j.jacbts.2018.01.015 Text en © 2018 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle PRECLINICAL RESEARCH
Heikal, Lamia
Starr, Anna
Hussein, Dania
Prieto-Lloret, Jesus
Aaronson, Phil
Dailey, Lea Ann
Nandi, Manasi
l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title_full l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title_fullStr l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title_full_unstemmed l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title_short l-Phenylalanine Restores Vascular Function in Spontaneously Hypertensive Rats Through Activation of the GCH1-GFRP Complex
title_sort l-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the gch1-gfrp complex
topic PRECLINICAL RESEARCH
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6018612/
https://www.ncbi.nlm.nih.gov/pubmed/29963647
http://dx.doi.org/10.1016/j.jacbts.2018.01.015
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