Big endothelin-1-induced sudden death is inhibited by phosphoramidon in mice.
The lethal activity of big endothelin-1 (bET-1) was examined in mice and compared with endothelin-1 (ET-1). Like ET-1, intravenous administration of bET-1 produced sudden death with an approximate LD50 value at 21.0 nmol/kg, higher than that of ET-1 (3.8 nmol/kg). At doses above the respective LD90 value, the latency to death was much longer in bET-1-treated mice with sustained elevation of plasma immunoreactive ET-1 (IR-ET-1). A metalloproteinase inhibitor, phosphoramidon, although failing to inhibit sudden death induced by ET-1, suppressed bET-1-induced lethality and elevation of plasma IR-ET-1 probably due to an inhibition of the enzymatic conversion of bET-1 to ET-1.
Matsuura
A
A
Pharmacology Department, Sapporo Breweries Ltd., Shizuoka, Japan.
Okumura
H
H
Ashizawa
N
N
Kobayashi
F
F
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003645:Death, Sudden; D004336:Drug Antagonism; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood / Q000494:pharmacology*; D006020:Glycopeptides / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D008297:Male; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors; D051379:Mice; D008813:Mice, Inbred ICR; D011498:Protein Precursors / Q000097:blood / Q000494:pharmacology*
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; D008666:Metalloendopeptidases; C008890:phosphoramidon