Effect of uric acid on hypertension progression in spontaneously hypertensive rats

Aims: We investigated the effects of soluble uric acid (UA) on the development of hypertension in spontaneously hypertensive rats (SHRs), using Wistar-Kyoto rats (WKY) as normotensive controls. Main methods: UA was prepared freshly as a suspension in saline solution and administered twice daily, intraperitoneally, at a dose of 250 mg/kg body weight for five weeks to SHR-UA (n = 7) and WKY-UA rats (n = 5). Controls for both strains were injected with saline solution (WKY-C and SHR-C, n = 5 each). Blood pressure, determined by tail-cuff plethysmography, levels of urine and blood biochemical parameters were monitored weekly. Oxidative stress, renal cytokines mRNA levels and immune cells infiltration were determined at the end of the study. Key findings: UA did not alter blood pressure in the WKY rats, but markedly prevented the development of hypertension in SHRs. Urine volume was significantly increased in the SHR-UA group. UA protected against renal oxidative stress as indicated by a decrease in MDA content in the SHR-UA group when compared to the SHR-C group: MDA content was unchanged in the WKY animals. Plasma antioxidant capacity decreased significantly in the SHR-UA animals when compared to the other three groups. There was a significant decrease in renal infiltrating lymphocytes in the SHR-UA treated animals. Changes in the expression of TNF-alpha, IL-2 and IL-6 were detected in the SHR-UA group. Significance: We conclude that UA protects against progression of hypertension in SHR rats. (C) 2010 Elsevier Inc. All rights reserved.