Abstract

Tetrahydrobiopterin (BH₄) is an essential cofactor of nitric oxide synthase (NOS). In the cardiovascular system, endothelial NOS (eNOS) has a major role in maintaining vascular tone and endothelial function, as well as in mediating many other vascular protective properties. Evidence from humans and animals have demonstrated that decreased BH₄ bioavailability, with subsequent uncoupling of eNOS, has significant effects on the pathogenesis of endothelial dysfunction, which is a hallmark of vascular injury in cardiovascular disorders, including hypertension, hyperlipidemia, and diabetes. In this review, we discuss the synthesis of BH₄, its molecular mechanisms regulating eNOS coupling, the pathophysiologic roles of decreased BH₄ bioavailability in cardiovascular diseases, and the potential therapeutic application of BH₄ in clinics.

Keywords: Tetrahydrobiopterin, endothelial nitric oxide synthase, endothelial function, eNOS uncoupling.