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-piperidinopyrimidine) depends upon aryl sulfotransferase (SULT1)-catalyzed sulfation for its bioactivation. Previous reports suggest that glucocorticoids induce class-specific SULT1 and isoform-specific SULT1A1 gene expression in rat liver. In the present study, rats were treated with the glucocorticoid triamcinolone acetonide (TA, 5 mg/kg/day i.p. x 3 days) or its vehicle, 2% Tween-20, prior to minoxidil, and subsequent effects on mean arterial pressure (MAP), heart rate (HR), and hepatic SULT1 gene expression were characterized. 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 following minoxidil injection. Pentachlorophenol (PCP, 40 micromol/kg i.p.), an inhibitor of SULT1 enzyme activity, effectively ablated the hypotensive effects of minoxidil. By contrast, pretreatment with TA significantly enhanced minoxidil-induced hypotension. Relative to vehicle-treated controls, TA-treated rats displayed a steeper rate of decline in MAP and more profound levels of hypotension with decreases in MAP following minoxidil administration of 27.8%. TA also produced significant increases in hepatic SULT1 mRNA expression (of 271%) and SULT1A1 immunoreactive protein levels (of 273%), relative to vehicle-treated controls. These results provide physiological evidence to support the biological relevance of SULT1A1 induction by glucocorticoids. The data indicate that steroid treatment induces SULT1A1 gene expression and, as a consequence, accentuates the hypotensive effects of minoxidil.
Duanmu
Z
Z
Institute of Chemical Toxicology, Wayne State University, Detroit, Michigan 48201, USA.
Dunbar
J
J
Falany
C N
CN
Runge-Morris
M
M
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D015239:Arylsulfotransferase / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects*; D004790:Enzyme Induction / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008297:Male; D008914:Minoxidil / Q000494:pharmacology*; D010416:Pentachlorophenol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014222:Triamcinolone Acetonide / Q000494:pharmacology*
D000959:Antihypertensive Agents; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; D008914:Minoxidil; D010416:Pentachlorophenol; D015239:Arylsulfotransferase; D014222:Triamcinolone Acetonide