Effects of sulfobromophthalein and ethacrynic acid on glyceryl trinitrate relaxation.
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.
Lau
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DT
Department of Pharmacy, School of Pharmacy, University of California, San Francisco 94143-0446.
Benet
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LZ
D000818:Animals; D001011:Aorta / Q000187:drug effects; D004976:Ethacrynic Acid / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D005996:Nitroglycerin / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology; D010656:Phenylephrine; D011817:Rabbits; D013448:Sulfobromophthalein / Q000494:pharmacology*; D014664:Vasodilation / Q000187:drug effects
D013448:Sulfobromophthalein; D010656:Phenylephrine; C014509:dinitroglycerol; D005982:Glutathione Transferase; D005996:Nitroglycerin; D004976:Ethacrynic Acid