Oxonic acid-induced hyperuricemia elevates plasma aldosterone in experimental renal insufficiency.

Background Hyperuricemia is associated with renal insufficiency and may predispose to Na + retention and hypertension. Whether hyperuricemia plays a causal role in the pathogenesis of cardiovascular disease remains controversial. Objective We examined the effects of hyperuricemia on circulating and renal components of the renin-angiotensin-aldosterone system in experimental renal insufficiency. Methods Three weeks after 5/6 nephrectomy or sham-operation, rats were put on 2.0% oxonic acid diet for 9 weeks. Blood pressure was monitored using tail-cuff, and blood, urine, and kidney samples were taken, as appropriate. Kidney angiotensin-converting enzyme , angiotensin-converting enzyme 2 and angiotensin II receptors (AT 1R , AT 2R ) were examined using real-time reverse transcriptase-PCR and autoradiography. Results Oxonic acid diet increased plasma uric acid by 80-90 μmol/l, while blood pressure was elevated only in hyperuricemic 5/6 nephrectomy rats (18 mmHg). Creatinine clearance was reduced by 60% in both 5/6 nephrectomy groups and by 25% in hyperuricemic Sham rats. The 5/6 nephrectomy group showed over 90% suppression of plasma renin activity, whereas the Sham + oxonic acid diet group showed 1.2 and 1.4-fold, and 5/6 nephrectomy + oxonic acid diet group 2.5 and 2.3-fold increases in plasma renin activity and plasma aldosterone, respectively. Hyperuricemia increased K + and decreased Na + excretion in Sham and 5/6 nephrectomy rats, leading to a more than 1.6-fold increase in urine K + to Na + ratio. No changes in kidney angiotensin-converting enzyme, angiotensin-converting enzyme 2, AT 1R or AT 2R were detected that could explain the hyperuricemia-induced alteration in Na + -K + balance. Conclusion As oxonic acid diet increased plasma renin activity, plasma aldosterone, and urine K + to Na + ratio, these changes may play a significant role in the harmful cardiovascular actions of hyperuricemia.