Mild hyperuricemia induces glomerular hypertension in normal rats.
Mildly hyperuricemic rats develop renin-dependent hypertension and interstitial renal disease. Hyperuricemia might also induce changes in glomerular hemodynamics. Micropuncture experiments under deep anesthesia were performed in Sprague-Dawley rats fed a low-salt diet (LS group), fed a low-salt diet and treated with oxonic acid (OA/LS group), and fed a low-salt diet and treated with oxonic acid + allopurinol (OA/LS/AP group) for 5 wk. The OA/LS group developed hyperuricemia and hypertension compared with the LS group: 3.1 +/- 0.2 vs. 1.1 +/- 0.2 mg/dl (P < 0.01) and 143 +/- 4 vs. 126 +/- 2 mmHg (P < 0.01). Hyperuricemic rats developed increased glomerular capillary pressure compared with the LS rats: 56.7 +/- 1.2 vs. 51.9 +/- 1.4 mmHg (P < 0.05). Pre- and postglomerular resistances were not increased. Histology showed afferent arteriolar thickening with increased alpha-smooth muscle actin staining of the media. Allopurinol prevented hyperuricemia (1.14 +/- 0.2 mg/dl), systemic (121.8 +/- 2.8 mmHg) and glomerular hypertension (50.1 +/- 0.8 mmHg), and arteriolopathy in oxonic acid-treated rats. Linear regression analysis showed that glomerular capillary pressure and arteriolar thickening correlated positively with serum uric acid and systolic blood pressure. Glomerular hypertension may be partially mediated by an abnormal vascular response to systemic hypertension due to arteriolopathy of the afferent arteriole.
Sánchez-Lozada
Laura G
LG
Department of Nephrology, Instituto Nacional de Cardiologia I Chavez, 14080 Mexico City, Mexico. lgsanchezlozada@hotmail.com
Tapia
Edilia
E
Avila-Casado
Carmen
C
Soto
Virgilia
V
Franco
Martha
M
Santamaría
José
J
Nakagawa
Takahiko
T
Rodríguez-Iturbe
Bernardo
B
Johnson
Richard J
RJ
Herrera-Acosta
Jaime
J
D000818:Animals; D001160:Arterioles / Q000473:pathology; D001794:Blood Pressure; D004195:Disease Models, Animal; D006977:Hypertension, Renal / Q000139:chemically induced / Q000209:etiology* / Q000473:pathology*; D006984:Hypertrophy; D007678:Kidney Glomerulus / Q000098:blood supply; D008297:Male; D010094:Oxonic Acid; D051381:Rats; D017207:Rats, Sprague-Dawley; D012079:Renal Circulation / Q000502:physiology; D014527:Uric Acid / Q000097:blood*
D014527:Uric Acid; D010094:Oxonic Acid