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Effects of sulfobromophthalein and ethacrynic acid on glyceryl trinitrate relaxation.

Biochemical pharmacology (1992-05-28)
D T Lau, L Z Benet
ABSTRACT

The effects of sulfobromophthalein (SBP) and ethacrynic acid (ECA), both inhibitors of glutathione S-transferase (GST), or glyceryl trinitrate (GTN)-induced vasorelaxation were investigated in rabbit aortic strips. The aortic strips were pre-contracted with phenylephrine, followed by relaxation with 0.5 microM GTN, with or without 0.1 mM SBP or ECA. ECA was observed to inhibit GTN relaxation approximately 32%, whereas SBP did not alter the GTN activity. The dinitrate metabolites (GDN) of GTN in the tissues were also measured. The amounts of both GDNs were decreased in the ECA-treated, but not the SBP-treated group. Moreover, in the ECA-treated group, a strong correlation was obtained between the loss of GTN activity and the decrease in GTN metabolism. Concentration-response studies also revealed that ECA attenuates GTN relaxation. The slope factor of the concentration-response curves was decreased by ECA, but not by SBP, although both inhibitors caused a mild decrease in Emax. In the 9000 g supernatant of rabbit aorta, ECA was also observed to inhibit GTN metabolism more significantly than SBP. The results suggest that the mechanism of GTN activation may involve a GST isozyme that possesses high activities towards ECA.

MATERIALS
Product Number
Brand
Product Description

Supelco
1,3-Dinitroglycerin solution, 1.0 mg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®
Supelco
1,3-Dinitroglycerin solution, 100 μg/mL in acetonitrile, ampule of 1 mL, certified reference material, Cerilliant®

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