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

Abstract

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.

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.

• Authors: Arttu Eräranta, Venla Kurra, Anna M Tahvanainen, Tuija I Vehmas, Peeter Kööbi, Päivi Lakkisto, Ilkka Tikkanen, Onni J Niemelä, Jukka T Mustonen, Ilkka H Pörsti
• Journal: Journal of hypertension (J Hypertens) Vol. 26 Issue 8 Pg. 1661-8 (Aug 2008) ISSN: 0263-6352 [Print] England
• PMID: 18622246 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Receptor, Angiotensin, Type 1
• Receptor, Angiotensin, Type 2
• Uric Acid
• Aldosterone
• Oxonic Acid

Topics

• Aldosterone (blood)
• Animal Feed
• Animals
• Autoradiography
• Blood Pressure
• Disease Models, Animal
• Hypertension, Renal (chemically induced, metabolism)
• Hyperuricemia (chemically induced, metabolism)
• Male
• Nephrectomy
• Oxonic Acid (toxicity)
• Rats
• Rats, Sprague-Dawley
• Receptor, Angiotensin, Type 1 (genetics, metabolism)
• Receptor, Angiotensin, Type 2 (genetics, metabolism)
• Renal Insufficiency, Chronic (chemically induced, metabolism)
• Renin-Angiotensin System (physiology)
• Reverse Transcriptase Polymerase Chain Reaction
• Uric Acid (blood)