Hyperuricemia has been associated with renal disease. Because glomerular hemodynamic
alterations critically contribute to initiation and progression of renal disease,
we evaluated the effect of mild hyperuricemia in glomerular microcirculatory changes
in rats under normal conditions and with renal injury induced by subtotal renal ablation
Hyperuricemia was induced in normal and remnant kidney (RK) rats on a normal sodium
diet by administration of oxonic acid (OA). To prevent hyperuricemia, allopurinol
(AP) was administered concomitantly. Glomerular hemodynamics were evaluated by micropuncture
techniques. Systolic blood pressure (SBP), proteinuria, arterial morphology, and serum
uric acid were measured. In RK rats, glomerulosclerosis, fibrosis, and inflammatory
cell infiltration (CD5+) were also assessed.
In normal rats, hyperuricemia resulted in afferent arteriole thickening associated
with renal cortical vasoconstriction [single nephron glomerular filtration rate (SNGFR)
-35%, P < 0.05) and glomerular hypertension (P < 0.05). Allopurinol treatment prevented
structural and functional alterations. In RK rats, hyperuricemia produced more renal
vascular damage than control animals coupled with severe cortical vasoconstriction
(SNGFR -40%, P < 0.05) and persistent glomerular hypertension. Allopurinol partially
prevented cortical vasoconstriction, and fully prevented arteriolopathy and glomerular
hypertension associated with significantly less infiltration of CD5+ cells.
Hyperuricemia induces arteriolopathy of preglomerular vessels, which impairs the autoregulatory
response of afferent arterioles, resulting in glomerular hypertension. Lumen obliteration
induced by vascular wall thickening produces severe renal hypoperfusion. The resulting
ischemia is a potent stimulus that induces tubulointerstitial inflammation and fibrosis,
as well as arterial hypertension. These studies provide a potential mechanism by which
hyperuricemia can mediate hypertension and renal disease.