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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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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. |
format | Online Article Text |
id | pubmed-6018612 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
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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