Is tetrahydrobiopterin a therapeutic option in diabetic hypertensive patients?

Alberto Francisco Rubio-Guerra1, Hilda Vargas-Robles2, Luz Maria Ramos-Brizuela1, Bruno Alfonso Escalante-Acosta21Metabolic Clinic, Hospital General de Ticomán SS DF, Mexico; 2Department of Molecular Biomedicine, Centro de Investigacion y de Estudios Avanzados del IPN, MexicoAbstract: Nitric oxide (NO) is an important regulator of vascular tone, and is also an antithrombotic, anti-inflammatory, antiproliferative, and antiatherogenic factor. Endothelial function is altered in patients with coronary artery disease, stroke, and peripheral artery disease, and endothelial dysfunction correlates with the risk factor profile for a patient. Hypertension and type 2 diabetes are risk factors for vascular disease, and are both pathologies characterized by loss of NO activity. Indeed, endothelial dysfunction is usually present in diabetic and/or hypertensive patients. Tetrahydrobiopterin is an essential cofactor for the NO synthase enzyme, and insufficiency of this cofactor leads to uncoupling of the enzyme, release of superoxide, endothelial dysfunction, progression of hypertension, and finally, proatherogenic effects. Tetrahydrobiopterin is also an important mediator of NO synthase regulation in type 2 diabetes and hypertension, and may be a rational therapeutic target to restore endothelial function and prevent vascular disease in these patients. The aim of this paper is to review the rationale for therapeutic strategies directed to biopterins as a target for vascular disease in type 2 diabetic hypertensive patients.Keywords: tetrahydrobiopterin, endothelial dysfunction, diabetes, hypertension, oxidative stress, nitric oxide, eNOS synthase uncoupling