Mild hyperuricemia induces vasoconstriction and maintains glomerular hypertension in normal and remnant kidney rats.
BACKGROUND
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 (RK).


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Sánchez-Lozada
Laura G
LG
Department of Nephrology, Instituto Nacional de Cardiología Ignacio Chavez, Mexico City, Mexico. lgsanchezlozada@hotmail.com
Tapia
Edilia
E
Santamaría
José
J
Avila-Casado
Carmen
C
Soto
Virgilia
V
Nepomuceno
Tomás
T
Rodríguez-Iturbe
Bernardo
B
Johnson
Richard J
RJ
Herrera-Acosta
Jaime
J
D000818:Animals; D001160:Arterioles / Q000473:pathology; D006978:Hypertension, Renovascular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D033461:Hyperuricemia / Q000150:complications / Q000473:pathology / Q000503:physiopathology*; D007678:Kidney Glomerulus / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009392:Nephrectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D012982:Sodium, Dietary / Q000008:administration & dosage; D014661:Vasoconstriction / Q000502:physiology*
D012982:Sodium, Dietary