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Am J Physiol Renal Physiol (June 26, 2002). doi:10.1152/ajprenal.00170.2002
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Articles in PresS, published online ahead of print June 26, 2002
Am J Physiol Renal Physiol, 10.1152/ajprenal.00170.2002
Submitted on May 1, 2002
Accepted on June 25, 2002

MILD HYPERURICEMIA INDUCES GLOMERULAR HYPERTENSION IN NORMAL RATS

Laura G. Sanchez-Lozada1*, Edilia Tapia1, Carmen Avila-Casado2, Virgilia Soto2, Martha Franco1, Jose Santamaria1, Takahiko Nakagawa3, Bernardo Rodriguez-Iturbe4, Richard J. Johnson3, and Jaime Herrera-Acosta1

1 Department of Nephrology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, D.F., Mexico
2 Department of Pathology, Instituto Nacional de Cardiologia Ignacio Chavez, Mexico City, D.F., Mexico
3 Division of Nephrology, Baylor College of Medicine, Houston, Texas, USA
4 Hospital Universitario, Universidad del Zulia, Maracaibo, Venezuela

* To whom correspondence should be addressed. E-mail: lgsanchezlozada{at}hotmail.com.

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 on low salt diet (LS), LS plus oxonic acid (LS/OA) and LS/OA plus allopurinol (LS/OA/AP) for 5 weeks. LS/OA group developed hyperuricemia and hypertension compared to LS rats (3.1±0.2 vs 1.1±0.2 mg/dL, p<0.01; 143±4 vs 126±2 mmHg, p<0.01). Hyperuricemic rats developed increased glomerular capillary pressure (Pgc) compared to LS animals (56.7±1.2 vs. 51.9 ± 1.4 mmHg, p<0.05). Pre and post glomerular 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) as well as arteriolopathy in OA treated rats. Linear regression analysis showed that Pgc and arteriolar thickening correlated positively with serum uric acid and with systolic blood pressure. Glomerular hypertension may be partially mediated by an abnormal vascular response to systemic hypertension due to arteriolopathy of the afferent arteriole.




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