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 (AT1R, AT2R) were examined using real-time reverse transcriptase-PCR and autoradiography.


RESULTS
Oxonic acid diet increased plasma uric acid by 80-90 micromol/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, AT1R or AT2R were detected that could explain the hyperuricemia-induced alteration in Na-K balance.


CONCLUSIONS
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.
Eräranta
Arttu
A
Institute of Medical Technology, Department of Internal Medicine, University of Tampere, Tampere, Finland.
Kurra
Venla
V
Tahvanainen
Anna M
AM
Vehmas
Tuija I
TI
Kööbi
Peeter
P
Lakkisto
Päivi
P
Tikkanen
Ilkka
I
Niemelä
Onni J
OJ
Mustonen
Jukka T
JT
Pörsti
Ilkka H
IH
D000450:Aldosterone / Q000097:blood*; D000821:Animal Feed; D000818:Animals; D001345:Autoradiography; D001794:Blood Pressure; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000139:chemically induced / Q000378:metabolism*; D033461:Hyperuricemia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009392:Nephrectomy; D010094:Oxonic Acid / Q000633:toxicity*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000235:genetics / Q000378:metabolism; D044139:Receptor, Angiotensin, Type 2 / Q000235:genetics / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000139:chemically induced / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014527:Uric Acid / Q000097:blood
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D014527:Uric Acid; D000450:Aldosterone; D010094:Oxonic Acid