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Abstract: SA-PO753

Effects of Hyperuricemia on the Progression of Salt-Sensitive (SS) Hypertension in Dahl SS Rats

Session Information

  • Hypertension and CVD: Mechanisms
    November 05, 2022 | Location: Exhibit Hall, Orange County Convention Center‚ West Building
    Abstract Time: 10:00 AM - 12:00 PM

Category: Hypertension and CVD

  • 1503 Hypertension and CVD: Mechanisms

Authors

  • Dissanayake, Lashodya Vindana, University of South Florida, Tampa, Florida, United States
  • Zietara, Adrian P., University of South Florida, Tampa, Florida, United States
  • Levchenko, Vladislav, University of South Florida, Tampa, Florida, United States
  • Palygin, Oleg, Medical University of South Carolina, Charleston, South Carolina, United States
  • Staruschenko, Alexander, University of South Florida, Tampa, Florida, United States
Background

Uric acid (UA) is a purine metabolite that has shown both oxidative and antioxidant properties. Increased plasma levels of UA (hyperuricemia) have been associated with hypertension and chronic kidney disease. Variations in dietary salt intake affect plasma and urine UA levels and may be involved in blood pressure and renal function control. We explore conditions of induced mild hyperuricemia and a high salt diet on the development of hypertension using Dahl SS rats, a model of salt-sensitive (SS) hypertension, and chronic administration of oxonic acid. Oxonic acid is a uricase inhibitor that prevents the breakdown of UA further into more soluble allantoin.

Methods

8-week-old Dahl SS male rats were implanted with telemeters. After recovery, BP measurements were collected for 4 days on a 0.4% NaCl diet and switched to either a 4% NaCl diet or a 2% oxonic acid + 4% NaCl diet (treatment, N=4-6) for 3 weeks. Rats were euthanized, and tissue, plasma, and urine were collected for the following analysis.

Results

Treatment with oxonic acid for 3-weeks increased plasma UA 5-fold (0.25±0.01 vs. 1.37±0.06 mg/dl, control vs. treated) while decreasing the urine UA excretion (0.33±0.01 vs. 0.19±0.01 UA/Cre). Elevated UA plasma levels were associated with significantly attenuated progression and magnitude of SS hypertension (mean arterial pressure: 159±1 vs. 137±1 mmHg, control vs. treated). Total body weight (TBW) and kidney weight/TBW ratio did not differ. The treatment group had a lower heart weight/TBW ratio (3.98±0.03 vs. 3.64±0.02). Overall, electrolyte homeostasis did not vary between the groups; however, urine Ca2+ excretion was significantly lower in the treatment group (1.48±0.09 vs.0.43±0.06 Ca2+/Cre).

Conclusion

The present study indicates that the increase in UA plasma levels attenuates the progression of SS hypertension. These results may suggest that UA homeostasis may be involved in the regulation of oxidative stress and has a protective effect against salt-induced hypertension.

Funding

  • Other NIH Support