Blood pressure response to ethanol in relation to acetaldehyde levels and dopamine-beta-hydroxylase activity in rats pretreated with disulfiram, cyanamide and coprine.
The blood pressure response after ethanol administration was studied in relation to blood acetaldehyde levels, aldehyde-dehydrogenase (ALDH)--and dopamine-beta-hydroxylase (DBH) activities in rats pretreated with the ethanol-sensitizing compounds disulfiram, cyanamide and coprine and the DBH-inhibitor FLA-57. Disulfiram, cyanamide and coprine, but not FLA-57, inhibited the low-Km ALDH in the liver and caused an increased acetaldehyde level in blood. Disulfiram and FLA-57, but not cyanamide and coprine, decreased the DBH-activity in the heart and the levels of norepinephrine in the heart and the brain. In disulfiram-treated rats with a low DBH-activity, a fall in blood pressure was observed at acetaldehyde levels being slightly higher than those found in control rats. In disulfiram-treated rats with a DBH-activity close to control activity and in rats pretreated with cyanamide or coprine, a fall in blood pressure were observed in rats pretreated with FLA-57. In rats pretreated with coprine + FLA-57, the fall in blood pressure was similar, or even lower, than in rats pretreated with coprine alone. The results suggest that acetaldehyde is the main determinant of the hypotension elicited by ethanol in rats pretreated with ALDH-inhibitors, and that the role of DBH in the disulfiram-ethanol reaction has been over-estimated in previous studies.
D000079:Acetaldehyde / Q000097:blood*; D000445:Aldehyde Oxidoreductases / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000378:metabolism; D003484:Cyanamide / Q000494:pharmacology*; D003486:Cyanides / Q000494:pharmacology*; D003521:Cyclopropanes / Q000494:pharmacology*; D004221:Disulfiram / Q000494:pharmacology*; D004298:Dopamine / Q000378:metabolism; D004299:Dopamine beta-Hydroxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000431:Ethanol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D005973:Glutamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009206:Myocardium / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D051381:Rats
D003486:Cyanides; D003521:Cyclopropanes; D005973:Glutamine; D000431:Ethanol; D003484:Cyanamide; D004299:Dopamine beta-Hydroxylase; D000445:Aldehyde Oxidoreductases; D000079:Acetaldehyde; D004221:Disulfiram; D004298:Dopamine; D009638:Norepinephrine