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L-phenylalanine restores vascular function in spontaneously hypertensive rats through activation of the GCH1-GFRP complex

Research output: Contribution to journalArticlepeer-review

Original languageEnglish
Pages (from-to)366-377
JournalJournal of the American College of Cardiology
Issue number3
Early online date30 May 2018
Accepted/In press24 Jan 2018
E-pub ahead of print30 May 2018


King's Authors


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 BH4. 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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