Xanthine oxidase activity in the dexamethasone-induced hypertensive rat.
Hypertension may be associated with an increase in oxidative stress as a possible mechanism for the increased vascular tone and organ injury. Previously, we reported an increased production of reactive oxygen species and endothelial cell death in the microcirculation of hypertensive rats. We hypothesize that xanthine oxidase (XO) may be a potential source of oxidants induced by glucocorticoid-induced hypertension. Male Wistar rats were administered dexamethasone (0.5 mg/kg/day) for 5 days to induce hypertension. After general anesthesia, cremaster muscle was collected for analysis of XO and xanthine dehydrogenase (XDH) activities. The mean blood pressure and XO levels in cremaster muscle were significantly increased in the dexamethasone-treated rats compared with controls. There was a strong age-dependent rise in total XO + XDH activity in all groups. To inhibit XO, we administered allopurinol (ALLO, 0.4 mg/mL) in the drinking water to a subset of control and dexamethasone-treated rats during a 5-day treatment. The ALLO significantly reduced the mean arterial blood pressure in the dexamethasone-treated rats. Although in the cremaster muscle the total XO + XDH levels were not completely reduced with ALLO, the XO levels of the dexamethasone-treated + ALLO rats were reduced to levels of the control + ALLO group. These results suggest that dexamethasone induces an elevated level of XO activity in the cremaster muscle. The enhanced XO activity can be attenuated by chronic allopurinol treatment.
Wallwork
Camille J
CJ
Department of Bioengineering, Whitaker Institute for Biomedical Engineering, University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0412, USA.
Parks
Dale A
DA
Schmid-Schönbein
Geert W
GW
D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure; D002851:Chromatography, High Pressure Liquid; D003907:Dexamethasone / Q000494:pharmacology*; D005609:Free Radicals; D005938:Glucocorticoids / Q000378:metabolism; D006973:Hypertension / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism; D016877:Oxidants / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D014968:Xanthine Dehydrogenase / Q000378:metabolism; D014969:Xanthine Oxidase / Q000378:metabolism*
D005609:Free Radicals; D005938:Glucocorticoids; D016877:Oxidants; D000493:Allopurinol; D003907:Dexamethasone; D014968:Xanthine Dehydrogenase; D014969:Xanthine Oxidase; D010100:Oxygen