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European journal of pharmacology

Renal effects of pinane-thromboxane A2 and indomethacin in saline volume-expanded spontaneously hypertensive rats.


PMID 7151863

Abstract

In 6-week old spontaneously hypertensive rats (SHR), indomethacin (5 mg/kg i.v.) and pinane-thromboxane A2 (PTA2) (50 micrograms/kg per h i.v.) a thromboxane A2 (TXA2) antagonist as well as a TXA2 synthetase inhibitor, resulted in natriuresis accompanied by an increase in p-aminohippuric acid and inulin clearances. Indomethacin acted as an antidiuretic in 6 week Wistar-Kyoto rats (WKY). PTA2 did not alter renal functions in either 6 week WKY and 18 week SHR. Basal urinary excretion of TXB2 (UTXB2V) was greater in 6 week SHR than in 6 week WKY and 18 week SHR, and that of 6-keto-PGF1 alpha (U6-keto-PGF1 alpha V) did not differ among these strains. Thus, U6-keto-PGF1 alpha V/UTXB2V was lower in the 6 week SHR. Basal urinary excretion of PGE (UPGEV) was much greater in 18 week SHR than in the 2 other groups. In the 6 week SHR, PTA2 decreased UTXB2V and increased U6-keto-PGF1 alpha V without affecting UPGEV, and indomethacin reduced UTXB2V more markedly than did U6-keto-PGF1 alpha V and UPGEV. Thus, both PTA2 and indomethacin increased U6-keto-PGF1 alpha V/UTXB2V in the 6 week SHR. These findings indicate that a disequilibrium in the biosynthesis of vasoconstrictive TXA2 and of vasodilator PGI2 may be involved in water and sodium retention in SHR during the developmental phase of hypertension.