Growth factor regulation of interleukin-1β-induced nitric oxide synthase and GTP:cyclohydrolase expression in cultured smooth muscle cells

Abstract

Induction of NO synthase expression by interleukin-1β in cultured vascular smooth muscle cells from rat aortas was accompanied by simultaneous induction of GTP:cyclohydrolase I. This enzyme regulates the de novo synthesis pathway for tetrahydrobiopterin, an essential cofactor for the catalytic conversion of L-arginine to L-citrulline and NO by inducible NO synthase. Inhibition of GTP:cyclohydrolase attenuated NO production by interleukin-1β-stimulated smooth muscle cells. Peptide growth factors such as fibroblast growth factor, platelet-derived growth factor and transforming growth factorβ1 and the protease thrombin have been shown to modulate the production NO by cytokine-treated smooth muscle cells. These peptide agonists also regulated the induction of NO synthase and GTP:cyclohydrolase mRNA expression.