Hyperuricemia and the renin-angiotensin-aldosterone system in experimental renal insufficiency
ERÄRANTA, ARTTU (2008)
2008
Biokemia - Biochemistry
Lääketieteellinen tiedekunta - Faculty of Medicine
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Hyväksymispäivämäärä
2008-06-09
Julkaisun pysyvä osoite on
https://urn.fi/urn:nbn:fi:uta-1-18749
https://urn.fi/urn:nbn:fi:uta-1-18749
Tiivistelmä
Background and Aims – 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. The aim of the study was to examine 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 (NX) or sham-operation, rats were put on 2.0% oxonic acid diet (Oxo) for 9 weeks. Blood pressure (BP) was monitored using tail-cuff, and blood, urine, and kidney samples were taken, as appropriate. Kidney angiotensin-converting enzymes (ACE, ACE2), and angiotensin II receptors (AT1R, AT2R) were examined using real-time RT-PCR and autoradiography, while plasma renin activity (PRA) and aldosterone were determined using radioimmunoassay.
Results – Oxo increased plasma uric acid as expected, while BP was elevated only in hyperuricemic NX rats. Creatinine clearance was reduced by 60% in both NX groups, and by 25% in hyperuricemic Sham rats. The NX group showed over 90% suppression of PRA, whereas Sham+Oxo group showed over 1.2-fold and NX+Oxo group over 2.3-fold increases in both PRA and plasma aldosterone. Hyperuricemia increased K+ and decreased Na+ excretion in Sham and NX rats, leading to over 1.6-fold increase in urine K+ to Na+ ratio. No changes in kidney ACE, ACE2, AT1R or AT2R were detected that could explain the hyperuricemia-induced alteration in Na+-K+ balance.
Conclusions – As oxonic acid diet increased PRA, plasma aldosterone, and urine K+ to Na+ ratio, these changes may play a significant role in the harmful cardiovascular actions of hyperuricemia.
Asiasanat: hyperuricemia, the renin-angiotensin-aldosterone system, chronic renal insufficiency
Methods – Three weeks after 5/6 nephrectomy (NX) or sham-operation, rats were put on 2.0% oxonic acid diet (Oxo) for 9 weeks. Blood pressure (BP) was monitored using tail-cuff, and blood, urine, and kidney samples were taken, as appropriate. Kidney angiotensin-converting enzymes (ACE, ACE2), and angiotensin II receptors (AT1R, AT2R) were examined using real-time RT-PCR and autoradiography, while plasma renin activity (PRA) and aldosterone were determined using radioimmunoassay.
Results – Oxo increased plasma uric acid as expected, while BP was elevated only in hyperuricemic NX rats. Creatinine clearance was reduced by 60% in both NX groups, and by 25% in hyperuricemic Sham rats. The NX group showed over 90% suppression of PRA, whereas Sham+Oxo group showed over 1.2-fold and NX+Oxo group over 2.3-fold increases in both PRA and plasma aldosterone. Hyperuricemia increased K+ and decreased Na+ excretion in Sham and NX rats, leading to over 1.6-fold increase in urine K+ to Na+ ratio. No changes in kidney ACE, ACE2, AT1R or AT2R were detected that could explain the hyperuricemia-induced alteration in Na+-K+ balance.
Conclusions – As oxonic acid diet increased PRA, plasma aldosterone, and urine K+ to Na+ ratio, these changes may play a significant role in the harmful cardiovascular actions of hyperuricemia.
Asiasanat: hyperuricemia, the renin-angiotensin-aldosterone system, chronic renal insufficiency