Role of xanthine oxidase in dexamethasone-induced hypertension in rats.
1. Glucocorticoid-induced hypertension (GC-HT) in the rat is associated with nitric oxide-redox imbalance. 2. We studied the role of xanthine oxidase (XO), which is implicated in the production of reactive oxygen species, in dexamethasone-induced hypertension (dex-HT). 3. Thirty male Sprague-Dawley rats were divided randomly into four treatment groups: saline, dexamethasone (dex), allopurinol plus saline, and allopurinol plus dex. 4. Systolic blood pressures (SBP) and bodyweights were recorded each alternate day. Thymus weight was used as a marker of glucocorticoid activity, and serum urate to assess XO inhibition. 5. Dex increased SBP (110 +/- 2-126 +/- 3 mmHg; P < 0.001) and decreased thymus (P < 0.001) and bodyweights (P" < 0.01). Allopurinol decreased serum urate from 76 +/- 5 to 30 +/- 3 micromol/L (P < 0.001) in saline and from 84 +/- 13 to 28 +/- 2 micromol/L in dex-treated (P < 0.01) groups. 6. Allopurinol did not prevent dex-HT. This, together with our previous findings that allopurinol failed to prevent adrenocorticotrophic hormone induced hypertension, suggests that XO activity is not a major determinant of GC-HT in the rat.
Ong
Sharon L H
SL
High Blood Pressure Research Unit, John Curtin School of Medical Research, Australian National University, Canberra, Australian Capital Territory, Australia.
Vickers
Janine J
JJ
Zhang
Yi
Y
McKenzie
Katja U S
KU
Walsh
Claire E
CE
Whitworth
Judith A
JA
D000284:Administration, Oral; D000493:Allopurinol / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003907:Dexamethasone / Q000008:administration & dosage* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology*; D007279:Injections, Subcutaneous; D008297:Male; D009929:Organ Size / Q000187:drug effects; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013950:Thymus Gland / Q000033:anatomy & histology / Q000187:drug effects; D014527:Uric Acid / Q000097:blood; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors / Q000378:metabolism* / Q000502:physiology
D000893:Anti-Inflammatory Agents; D014527:Uric Acid; D000493:Allopurinol; D003907:Dexamethasone; D014969:Xanthine Oxidase