Our studies are focused on the role of nitric oxide in regulation of vasomotor function of cerebral arteries. A potent vasodilator, nitric oxide, is produced in endothelium by activation of nitric oxide synthase, an enzyme that converts L-arginine into nitric oxide and citrulline. Three distinct genes encoding nitric oxide synthase isoforms have been identified by molecular cloning techniques. Endothelial and neuronal isoform are constitutively expressed in endothelium and perivascular nerves, respectively. Inducible nitric oxide synthase is expressed in smooth muscle cells following activation with proinflammatory stimuli.

Activity of nitric oxide synthase(s) requires the presence of optimal concentrations of tetrahydrobiopterin as a cofactor. GTP cyclohydrolase I is a key enzyme in the synthesis of tetrahydrobiopterin. Our interest has been focused on the role of tetrahydrobiopterin in the regulation of endothelial function and the mechanism controlling mRNA expression and the activity of GTP cyclohydrolase I. These studies are closely related to our interest in optimal conditions required for expression and function of recombinant endothelial nitric oxide synthase gene. We are using adenoviral vectors to transfer nitric oxide synthase gene and restore production of nitric oxide in diseased blood vessels.