Thromboxane synthetase inhibitor UK38,485 lowers blood pressure in the adult spontaneously hypertensive rat

Treatment of young spontaneously hypertensive rats (SHR) with a thromboxane synthetase inhibitor (TSI) attenuates their subsequent development of hypertension. In this study, treatment of adult SHR during the established phase of hypertension with the TSI UK38,485 (100 mg/kg daily) lowered systolic blood pressure from baseline after 4 days of treatment to a maximum depression of 25 mm Hg on day 10 of the study. Additional confirmation of the fact that this TSI does not lower blood pressure acutely was made via continuous intraarterial recordings in SHR administered their first dose of UK38,485. Urinary dinor-6-keto-PGF1 alpha excretion was measured by a highly specific chemical-ionization, negative-ion GC/MS assay in the selective ion monitoring mode. This metabolite of PGI2 was not significantly affected by 6 days of daily administration of UK38,485 to adult SHR and implies that there was not sufficient endoperoxide shunting to affect total body PGI2 production. The finding that UK38,485 exhibited antihypertensive activity during established SHR hypertension was unexpected and has considerable practical and theoretical significance.