460 EFFECTS OF URIC ACID ON SYSTEMIC AND RENAL HEMODYNAMICS IN CONSCIOUS RABBITS

Abstract

Objectives: Experimental animal studies demonstrate that chronic hyperuricemia can induce renal damage as well as elevate blood pressure. This study was designed to investigate the influences of uric acid (UA) on renal hemodynamics in conscious animals. Design and Methods: In 8 conscious rabbits, renal plasma flow (RPF) and glomerular filtration rate (GFR) (estimated by clearance of para-aminohippurate and inulin, respectively) were measured at 20-min intervals before and after the intracutaneous administration of the following drugs at three occasions separately at least 1 week apart: (1) vehicle, (2) oxonic acid (i.e., uricase inhibitor) at 500 mg/kg of BW, (3) oxonic acid at 500 mg/kg of BW plus allopurinol (i.e., xanthine oxidase inhibitor) at 6 mg/kg of BW. Results: Serum UA, blood pressure (BP), pulse rate (PR), RPF and GFR remained unchanged after vehicle. Following the administration of oxonic acid, both BP and PR increased (115 ± 4/88 ± 2 to 126 ± 3/96 ± 1 mmHg, 229 ± 6 to 251 ± 4 /min) concomitantly with the elevation of serum UA (0.19 ± 0.03 to 0.40 ± 0.04 mg/dL). Additionally, RPF decreased (22 ± 2 to 17 ± 1 mL/min/kg of BW) without changes in GFR (3.7 ± 0.2 to 3.7 ± 0.1 mL/min/kg of BW). Consequently, oxonic acid increased filtration fraction (0.18 ± 0.01 to 0.21 ± 0.01). In contrast, allopurinol completely abolished all the changes induced by oxonic acid in serum UA, systemic hemodynamics and renal function. Conclusions: These results indicate that increased serum UA induced renovasoconstriction as well as elevated systemic pressure, and suggest that the renovasoconstriction induced by UA might occur mainly on the efferent arteriole.