Inhibition of biological actions of big endothelin-1 by phosphoramidon.
Endothelin (ET)-1 and big ET-1 both caused contraction of isolated porcine coronary arteries, but the potency of big ET-1 was 1/100-1/200 that of ET-1. These responses were independent of the vascular endothelium. Phosphoramidon blocked the vasoconstriction caused by 30 nM big ET-1, but was ineffective on the action of 0.3 nM ET-1. Also in vivo, phosphoramidon had no effect on the ET-1-induced pressor actions, but blocked the pressor and airway-contractile responses to big ET-1 in rats and/or guinea pigs. Thus, it is likely that the vascular responses to exogenous big ET-1 are at least in part due to its conversion to ET-1 by a phosphoramidon-sensitive ET converting enzyme(s) in the vascular smooth muscle in vitro and in vivo.
Fukuroda
T
T
Central Research Laboratories, Banyu Pharmaceutical Co., Ltd., Tokyo, Japan.
Noguchi
K
K
Tsuchida
S
S
Nishikibe
M
M
Ikemoto
F
F
Okada
K
K
Yano
M
M
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003331:Coronary Vessels / Q000187:drug effects / Q000502:physiology*; D019332:Endothelin-1; D016232:Endothelins / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D006020:Glycopeptides / Q000494:pharmacology*; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D012137:Respiratory System / Q000187:drug effects*; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects*
D019332:Endothelin-1; D016232:Endothelins; D006020:Glycopeptides; D011498:Protein Precursors; C008890:phosphoramidon