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.
D015121:6-Ketoprostaglandin F1 alpha / Q000652:urine; D000818:Animals; D015232:Dinoprostone; D011464:Epoprostenol / Q000096:biosynthesis; D007093:Imidazoles / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism*; D008297:Male; D011458:Prostaglandins E / Q000652:urine; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000652:urine*; D012965:Sodium Chloride / Q000378:metabolism / Q000494:pharmacology; D013928:Thromboxane A2 / Q000096:biosynthesis*; D013929:Thromboxane B2 / Q000652:urine; D013931:Thromboxanes / Q000096:biosynthesis*
D007093:Imidazoles; D011458:Prostaglandins E; D013931:Thromboxanes; D012965:Sodium Chloride; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; C029899:imidazole; D012964:Sodium; D011464:Epoprostenol; D015232:Dinoprostone