BACKGROUND: In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHF patients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. METHODS AND RESULTS: In 10 CHF patients with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 microg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemic patients (P<0.05). In a double-blind, crossover design, hyperuricemic CHF patients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743 micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05). CONCLUSIONS: In hyperuricemic CHF patients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.
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BACKGROUND: In patients with chronic heart failure (CHF), hyperuricemia is a common finding and is associated with reduced vasodilator capacity and impaired peripheral blood flow. It has been suggested that the causal link of this association is increased xanthine oxidase (XO)-derived oxygen free radical production and endothelial dysfunction. We therefore studied the effects of XO inhibition with allopurinol on endothelial function and peripheral blood flow in CHFpatients after intra-arterial infusion and after oral administration in 2 independent placebo-controlled studies. METHODS AND RESULTS: In 10 CHFpatients with normal serum uric acid (UA) levels (315+/-42 micromol/L) and 9 patients with elevated UA (535+/-54 micromol/L), endothelium-dependent (acetylcholine infusion) and endothelium-independent (nitroglycerin infusion) vasodilation of the radial artery was determined. Coinfusion of allopurinol (600 microg/min) improved endothelium-dependent but not endothelium-independent vasodilation in hyperuricemicpatients (P<0.05). In a double-blind, crossover design, hyperuricemic CHFpatients were randomly allocated to allopurinol 300 mg/d or placebo for 1 week. In 14 patients (UA 558+/-21 micromol/L, range 455 to 743 micromol/L), treatment reduced UA by >120 micromol/L in all patients (mean reduction 217+/-15 micromol/L, P<0.0001). Compared with placebo, allopurinol improved peak blood flow (venous occlusion plethysmography) in arms (+24%, P=0.027) and legs (+23%, P=0.029). Flow-dependent flow improved by 58% in arms (P=0.011). Allantoin, a marker of oxygen free radical generation, decreased by 20% after allopurinol treatment (P<0.001). There was a direct relation between change of UA and improvement of flow-dependent flow after allopurinol treatment (r=0.63, P<0.05). CONCLUSIONS: In hyperuricemic CHFpatients, XO inhibition with allopurinol improves peripheral vasodilator capacity and blood flow both locally and systemically.
Authors: Gregory D Lewis; Laurie Farrell; Malissa J Wood; Maryann Martinovic; Zoltan Arany; Glenn C Rowe; Amanda Souza; Susan Cheng; Elizabeth L McCabe; Elaine Yang; Xu Shi; Rahul Deo; Frederick P Roth; Aarti Asnani; Eugene P Rhee; David M Systrom; Marc J Semigran; Ramachandran S Vasan; Steven A Carr; Thomas J Wang; Marc S Sabatine; Clary B Clish; Robert E Gerszten Journal: Sci Transl Med Date: 2010-05-26 Impact factor: 17.956
Authors: Guanghong Jia; Javad Habibi; Brian P Bostick; Lixin Ma; Vincent G DeMarco; Annayya R Aroor; Melvin R Hayden; Adam T Whaley-Connell; James R Sowers Journal: Hypertension Date: 2014-12-08 Impact factor: 10.190