This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Thiazide diuretics when used in the treatment of hypertension are associated with many metabolic side effects including hyperuricemia, gout, insulin resistance, and hyperlipidemia. Each of these conditions is already highly prevalent in African-Americans. Our hypothesis is that thiazide-induced hyperuricemia decreases the efficacy of thiazides in controlling BP, leads to endothelial dysfunction, and increases the incidence of insulin resistance and impaired glucose tolerance. This hypothesis will be tested in a randomized double-blind placebo-controlled 2 [unreadable] 2 factorial clinical trial of 8-week duration in which a total of 300 African-Americans patients with stage 1 hypertension, BP: 140-159/90-99 mm Hg, will be assigned to one of four regimens: a thiazide-like diuretic, chlorthalidone 25 mg/day, and a xanthine oxidase inhibitor, allopurinol; chlorthalidone 25 mg/day and placebo; placebo; or allopurinol in conjunction with a low-sodium diet. The primary end-point is reduction in systolic BP. Secondary end-points measure endothelial function, ambulatory blood pressure, body composition, systemic inflammation, metabolic parameters, oxidant stress and renal hemodynamics.