Glucocorticoids inhibit tetrahydrobiopterin-dependent endothelial function

Douglas G. Johns, Anne M. Dorrance, Nicole L. Tramontini, R. Clinton Webb

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

Tetrahydrobiopterin (BH4) acts as an important co-factor for endothelial nitric oxide synthase (eNOS). Glucocorticoids have been shown to inhibit expression of the rate-limiting enzyme for tetrahydrobiopterin synthesis, GTP cyclohydrolase, in other cell types. We hypothesized that endothelium-dependent vasodilator responses would be blunted in rats made hypertensive with dexamethasone. Further, we hypothesized that treatment of rat vascular segments with dexamethasone would result in attenuation of endothelial function accompanied by decreased GTP cyclohydrolase expression. We report that endothelium-dependent relaxation responses to the calcium ionophore A23187 are reduced in aortic rings from dexamethasone-hypertensive rats compared with sham values. Dexamethasone incubation abolishes contraction to Nω-nitro-L-arginine (L-NNA, 10-5M) in endothelium-intact aortic rings, and inhibits expression of GTP cyclohydrolase. We conclude that inhibition of BH4 synthesis by glucocorticoid regulation of GTP cyclohydrolase expression may contribute to reduced endothelium-dependent vasodilation characteristic of glucocorticoid-induced hypertension.

Original languageEnglish (US)
Pages (from-to)27-31
Number of pages5
JournalProceedings of the Society for Experimental Biology and Medicine
Volume226
Issue number1
StatePublished - Jan 23 2001

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Keywords

  • Endothelial nitric oxide synthase
  • Glucocorticoids
  • Tetrahydrobiopterin

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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