Effect of some substituted pyrimidines on development of desoxycorticosterone-induced hypertension in rats

Chronic (15-week) dietary administration of 2-thio-6-aminouracil (TAU, 1.0 and 2.0 g/kg food) provided significant protection against elevation of blood pressure and cardiac hypertrophy in male rats treated with desoxycorticosterone trimethylacetate (DTMA) (5.0 mg twice weekly for 10 weeks). Assessment of thyroid activity was made by measurement of 24 h 131I uptake by the thyroid gland, PBI concentration of serum, rate of oxygen consumption, hematocrit ratio, hemoglobin concentration, and thyroid weight. By all these criteria, the rats given either dose of TAU were hypothyroid. In contrast chronic (17-week) dietary administration of 5-carboxy-2-thiouracil (0.50 and 1.00 g/kg food) and 5-carboxy-4-hydroxy-2-thiouracil (2.00 g/kg food) provided minimal protection against elevation of blood pressure and cardiac hypertrophy in male DTMA-treated rats. These compounds appeared to possess little or no antithyroid activity at the doses used. The results suggest a rough correlation between the degree of hypothyroidism produced by the compounds and their effectiveness in preventing rise of blood pressure in DTMA-treated rats.