Selective inhibition of renal thromboxane biosynthesis increased sodium excretion rate in normal and saline-loaded rats.

The excretion rates of renal thromboxane B2 (TXB2) and 6-ketoPGF1 alpha, the stable chemical metabolites of thromboxane A2 (TXA2) and prostaglandin I2 (PGI2) respectively, PGE2 and sodium were determined in normal and saline-loaded rats treated with the thromboxane synthetase inhibitor imidazole. In normal rats the administration of imidazole in doses which did not affect renal 6-keto-PGF1 alpha and PGE2 excretion but selectively inhibited renal TXB2 excretion, significantly increased the sodium excretion rate. Volume expansion with saline increased renal PGE2 and 6-ketoPGF1 alpha excretion but did not alter renal TXB2 excretion. The increase in renal prostaglandin excretion was accompanied by an increased sodium excretion rate. The administration of imidazole to saline-loaded animals also decreased renal TXB2 excretion but did not alter the increased excretion of renal PGE2 and 6-ketoPGF1 alpha. This reduction in renal thromboxane biosynthesis by imidazole further increased the sodium excretion rate. We suggest that TXA2 is a potent antinatriuretic factor as well as the most potent vasoconstrictor agent known.