Hyperuricemia induced by some antihypertensives and uricosuric drugs in oxonate-treated rats.

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Abstract
Effects of antihypertensive and uricosuric drugs were studied on the plasma and urinary levels of uric acid in oxonate-treated rats. Animals with a catheterized aorta were used to successively collect blood samples and this procedure simplified the evaluation of progressive changes of plasma uric acid, under successive loading with potassium oxonate. The plasma uric acid level of the oxonate-treated rats was increased with a single administration of diuretic chlorothiazides, furosemide, diazoxide and uricosuric drugs such as tienilic acid and probenecid. A well-maintained plasma uric acid level was produced by exogenously administered uric acid in rats which were given allopurinol and potassium oxonate. Diazoxide, tienilic acid and probenecid increased the plasma uric acid while diuretic chlorothiazides did not. Furosemide tended to decrease the plasma uric acid level at the early stage of administration to rats treated with allopurinol, oxonate and uric acid, but increased these levels several hours later when the effect was studied by uric acid loading test with rats treated with allopurinol and oxonate. These effects appeared as changes in the urine-excreted uric acid. The oxonate-treated rats demonstrated an acutely induced hyperuricemia with certain antihypertensives and with uricosuric drugs. The utility of these procedures for evaluating the hyperuricemic and uricosuric effects of drugs is discussed.

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