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...

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Published in:American journal of physiology. Renal physiology 2002-11, Vol.283 (5), p.F1105-F1110
Main Authors: Sánchez-Lozada, Laura G, Tapia, Edilia, Avila-Casado, Carmen, Soto, Virgilia, Franco, Martha, Santamaría, José, Nakagawa, Takahiko, Rodríguez-Iturbe, Bernardo, Johnson, Richard J, Herrera-Acosta, Jaime
Format: Article
Language:English
Subjects:
Animals
Arterioles - pathology
Blood Pressure
Disease Models, Animal
Hypertension, Renal - chemically induced
Hypertension, Renal - etiology
Hypertension, Renal - pathology
Hypertrophy
Kidney Glomerulus - blood supply
Male
Oxonic Acid
Rats
Rats, Sprague-Dawley
Renal Circulation - physiology
Uric Acid - blood
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Summary: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.
ISSN:1931-857X
1522-1466
DOI:10.1152/ajprenal.00170.2002