Induction of rat hepatic aryl sulfotransferase (SULT1A1) gene expression by triamcinolone acetonide: Impact on minoxidil-mediated hypotension

The hypotensive agent minoxidil (6-imino-1,2-dihydro-1-hydroxy-2-imino-4-pi peridinopyrimidine) depends upon aryl sulfotransferase (SULT1)-catalyzed su lfation for its bioactivation. Previous reports suggest that glucocorticoid s induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocortico id triamcinolone acetonide (TA, 5 mg/kg/day ip x 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pres sure (MAP), heart rate (HR), and hepatic SULT1 gene expression were charact erized. Minoxidil treatment (1.5 mg/kg) resulted in a steady decline in MAP values of 16.3 to 18.6% relative to basal control levels at 35 to 60 min f ollowing minoxidil injection. Pentachlorophenol (PCP, 40 mu mol/kg ip), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive eff ects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-tr eated rats displayed a steeper rate of decline in MAP and more profound lev els of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA exp ression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), rela tive to vehicle-treated controls. These results provide physiological evide nce to support the biological relevance of SULT1A1 induction by glucocortic oids. The data indicate that steroid treatment induces SULT1A1 gene express ion and, as a consequence, accentuates the hypotensive effects of minoxidil . (C) 2000 Academic Press.