Current Hypertension Reviews

Prof. Kazuomi Kario
Jichi Medical University
School of Medicine
Tochigi
Japan

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Glucocorticoid-Induced Hypertension and Tetrahydrobiopterin (BH4), a Common Cofactor for the Production of Vasoactive Molecules

Author(s): Brett M. Mitchell, Clinton Webb.

Abstract:

Excess glucocorticoids, whether produced endogenously or over-prescribed for immunosupression and antiinflammation, can lead to hypertension and cardiovascular disease. Humans and animals with glucocorticoid-induced hypertension exhibit reduced nitric oxide (NO) and serotonin, and have increased sensitivity to catecholamines. The common cofactor for the production of these vasoactive molecules is tetrahydrobiopterin (BH4). Recent research has focused on the effects of excess glucocorticoids on BH4 biosynthesis because reduced BH4 cofactor levels can alter the production of NO, serotonin, and catecholamines by NO synthase and the aromatic amino acid hydroxylases. This review will focus on the mechanisms and consequences of excess glucocorticoids on the BH4 biosynthesis pathway and the enzymes that utilize BH4 as a cofactor. Alterations in the production of BH4 contribute to glucocorticoid-induced hypertension and an understanding of the mechanisms may provide therapeutic targets to either develop synthetic glucocorticoids that do not affect BH4 biosynthesis or increase BH4 levels in conditions where glucocorticoids are elevated.

Keywords: gtp cyclohydrolase 1, tetrahydrobiopterin, glucocorticoids, endothelial nitric oxide synthase, endothelium

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Article Details

VOLUME: 1
ISSUE: 1
Year: 2005
Page: [1 - 6]
Pages: 6
DOI: 10.2174/1573402052952816