title: Allopurinol does not decrease blood pressure or prevent the development of hypertension in the deoxycorticosterone acetate-salt rat model.
abstract: Reactive oxygen species play an important role in the pathogenesis of hypertension, disease in which reactive oxygen species levels and markers of oxidative stress are increased. Xanthine oxidase (XO) is a reactive oxygen species-producing enzyme the activity of which may increase during hypertension. Studies on XO inhibition effects on blood pressure have yielded controversial results. We hypothesized that XO inhibition would decrease blood pressure or attenuate the development of deoxycorticosterone acetate (DOCA)-salt hypertension. We administered the XO inhibitor, allopurinol (50 mg/kg per day, orally) or its vehicle to rats during the established or development stages of DOCA-salt hypertension. We validated XO inhibition by high-performance liquid chromatography measurements of XO metabolites in urine, serum, and tissues demonstrating a decrease in products, increase in substrates, and detection of the active metabolite of allopurinol, oxypurinol. We monitored blood pressure continuously through radiotelemetry and performed gross evaluations of target organs of hypertension. Allopurinol treatment did not impact the course of DOCA-salt hypertension regardless of the timing of administration. Aside from a significant decrease in pulse pressure in allopurinol-treated rats, no positive differences were observed between the allopurinol and the vehicle-treated rats. We conclude that XO does not play an important role in the development or maintenance of hypertension in the rat DOCA-salt hypertension model.
authors.affiliation: Pharmacology and Toxicology Department, Michigan State University, East Lansing, MI 48824-1317, USA. szasziri@msu.edu
authors.forename: Theodora
authors.initials: T
authors.lastname: Szasz
authors.forename: A Elizabeth
authors.initials: AE
authors.lastname: Linder
authors.forename: Robert P
authors.initials: RP
authors.lastname: Davis
authors.forename: Robert
authors.initials: R
authors.lastname: Burnett
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Fink
authors.forename: Stephanie W
authors.initials: SW
authors.lastname: Watts
mesh_terms: D000493:Allopurinol / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects* / Q000502:physiology; D003900:Desoxycorticosterone / Q000633:toxicity*; D004195:Disease Models, Animal; D004791:Enzyme Inhibitors / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D006973:Hypertension / Q000139:chemically induced / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D003900:Desoxycorticosterone; D000493:Allopurinol; D014969:Xanthine Oxidase