Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.

@article{citeulike:2768037, abstract = {BACKGROUND: Experimentally-induced hyperuricaemia [due to inhibition of uricase with oxonic acid (OA)] in rats causes hypertension and renal alterations which can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an investigational, nonpurine and selective xanthine oxidase inhibitor, is a more effective UA-lowering agent than allopurinol. We therefore tested the hypothesis that Fx might be useful in treating hyperuricemia-induced hypertension and renal damage. METHODS: Four groups of male rats were studied: OA (750 mg/kg by daily gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n = 10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks after initiation of the study. Two groups of normal (N) rats were studied as controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting plasma UA were measured in all animals at baseline and at 4 and 8 weeks. Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks followed by histological evaluation of glomerular and afferent arteriole morphologies. RESULTS: In OA-induced hyperuricaemic rats, Fx lowered UA and ameliorated systemic and glomerular hypertension as well as mesangial matrix expansion and the development of preglomerular arteriolar disease as indicated by a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx tended to lower UA and had no effect on blood pressure, renal hemodynamics and afferent arteriole morphology. CONCLUSION: These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia.}, address = {Department of Nephrology, Instituto Nacional de Cardiologi\'{a} Ignacio Chavez, Juan Badiano 1, 14080-Mexico City, Mexico. lgsanchezlozada@hotmail.com}, author = {S\'{a}nchez-Lozada, L. G. and Tapia, E. and Soto, V. and Avila-Casado, C. and Franco, M. and Zhao, L. and Johnson, R. J. }, citeulike-article-id = {2768037}, issn = {1460-2385}, journal = {Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association}, month = {April}, number = {4}, pages = {1179--1185}, posted-at = {2008-05-08 09:12:42}, priority = {2}, title = {Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia.}, url = {http://view.ncbi.nlm.nih.gov/pubmed/18048425}, volume = {23}, year = {2008} }

TY - JOUR ID - citeulike:2768037 L3 - citeulike-article-id:2768037 TI - Treatment with the xanthine oxidase inhibitor febuxostat lowers uric acid and alleviates systemic and glomerular hypertension in experimental hyperuricaemia. JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association VL - 23 IS - 4 SP - 1179 EP - 1185 AD - Department of Nephrology, Instituto Nacional de Cardiologiá Ignacio Chavez, Juan Badiano 1, 14080-Mexico City, Mexico. lgsanchezlozada@hotmail.com SN - 1460-2385 N2 - BACKGROUND: Experimentally-induced hyperuricaemia [due to inhibition of uricase with oxonic acid (OA)] in rats causes hypertension and renal alterations which can be prevented by lowering uric acid (UA) with allopurinol. Febuxostat (Fx), an investigational, nonpurine and selective xanthine oxidase inhibitor, is a more effective UA-lowering agent than allopurinol. We therefore tested the hypothesis that Fx might be useful in treating hyperuricemia-induced hypertension and renal damage. METHODS: Four groups of male rats were studied: OA (750 mg/kg by daily gavage) was given for 8 weeks and Fx (5-6 mg/kg/day in drinking water; OA+Fx: n = 10) or placebo (OA+P: n = 11) were administered for 4 weeks beginning at 4 weeks after initiation of the study. Two groups of normal (N) rats were studied as controls (N+P and N+Fx: n = 10/group). Systolic blood pressure (SBP) and fasting plasma UA were measured in all animals at baseline and at 4 and 8 weeks. Glomerular haemodynamics by micropuncture techniques were determined at 8 weeks followed by histological evaluation of glomerular and afferent arteriole morphologies. RESULTS: In OA-induced hyperuricaemic rats, Fx lowered UA and ameliorated systemic and glomerular hypertension as well as mesangial matrix expansion and the development of preglomerular arteriolar disease as indicated by a reduction of the arteriolar area and media-to-lumen ratio. In normal rats, Fx tended to lower UA and had no effect on blood pressure, renal hemodynamics and afferent arteriole morphology. CONCLUSION: These results suggest that Fx merits further evaluation for the treatment of hypertension and renal alterations induced by hyperuricaemia. AU - Sánchez-Lozada, LG AU - Tapia, E AU - Soto, V AU - Avila-Casado, C AU - Franco, M AU - Zhao, L AU - Johnson, RJ PY - 2008/04// UR - http://view.ncbi.nlm.nih.gov/pubmed/18048425 ER -