Therapeutic Research

Abstract

Background and Objectives：Losartan promotes uric acid excretion and lowers serum uric acid levels by inhibiting URAT－1 and reduction of its URAT－1 mRNA level. However, few studies have assessed the effects of high－dose losartan on uric acid levels and adipokine after switching from other ARBs. In this study, the switching effect from other ARBs to high－dose losartan was evaluated in essential hypertensive patients with high serum uric acid levels（sUA＞6 mg／dL）. Subjects and Results：After screening sixty seven patients with high serum uric acid levels（sUA＞6 mg／dL）on treatment with an oral ARB, thirty seven patients who gave written informed consent were enrolled and thirty five patients completed this study. The background data of the subjects（mean age：69±13 years, 74％ men, and mean BMI：23± 5 kg／m2） and their main comorbidities （diabetes mellitus：29％, abnormal lipid metabolism：80％）indicated that this group of patients were hypertensive patients with mild to moderate risk. After 6 months of high dose losartan treatment, no change of blood pressure and pulse rate were observed （137±17／77±15 mmHg to 136±19／77±14mmHg, 68±12 bpm to 71±16 bpm）. The uUA／uCr ratio increased from 0.481 to 0.631（p ＜0.05）, sUA significantly decreased from 7.3 to 6.0 mg／dL（p＜0.001）. No significant changes in inflammatory cytokines（TNF－α, MCP－1, VCAM－1）were observed, high molecular weight（HMW）－adiponectin increased from 2,374 to 2,975 ng／mL（p＝0.039）. Conclusion：Switching to high－dose losartan from other ARBs resulted in uricosuric effect without significant change of blood pressure. Beneficial increase of HMW－adiponectin was also observed. These results provided that the use of high－dose losartan was beneficial in hypertensive patients with higher sUA.