Tetrahydrobiopterin, nitric oxide and regulation of cerebral arterial tone

Hiroyuki Kinoshita, Masato Tsutsui, Sheldon Milstien, Zvonimir S. Katusic

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


Tetrahydrobiopterin is an essential cofactor required for activity of nitric oxide synthases. Existing evidence suggests that, during activation of constitutive and inducible isoforms of nitric oxide synthase, tetrahydrobiopterin is needed for allosteric and redox activation of enzymetic activity. However, precise mechanisms underlying the role of tetrahydrobiopterin in regulation of nitric oxide formation is not fully understood. In cerebral and peripheral arteries, increased availability of tetrahydrobiopterin can augment production of nitric oxide. In contrast, in arteries depleted of tetrahydrobiopterin, production of nitric oxide is impaired. Proinflammatory cytokines enhance mRNA expression of the rate- limiting enzyme of tetrahydrobiopterin biosynthesis. GTP cyclohydrolase I and stimulate production of tetrahydrobiopterin. The ability of vascular tissues to synthesize tetrahydrobiopterin plays an important role in regulation of nitric oxide synthase under physiological conditions as well as during inflammation and sepsis. More recent studies concerning expression and function of recombinant nitric oxide synthases suggest that availability of tetrahydrobiopterin is important for production of nitric oxide in genetically engineered blood vessels. In this review, mechanisms regulating availability of intracellular tetrabydrobiopterin and its role in control of vascular tone under physiological and pathological conditions will be discussed.

Original languageEnglish (US)
Pages (from-to)295-302
Number of pages8
JournalProgress in Neurobiology
Issue number4
StatePublished - Jul 1997

ASJC Scopus subject areas

  • Neuroscience(all)


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