Investigation on inhibition of biological effects of endothelin.
The effects of a series of substances on the biological function of endothelin (ET) are reported. The substances used are: synthetic inhibitors of endothelium derived relaxing factors (EDRFs), inhibitor of big-endothelin converting enzyme phosphoramidon, antiserum of endothelin, antagonists of endothelin A receptor BQ123 and JKC301, and two Chinese anti-snake venom herb medicines Lobelia radicans Thumb and Taris polyphylla Smith var. chinensis (Franch) Hara. The results showed that inhibiting the production of nitric oxide (NO) could stimulate ET release from vascular endothelium, elevate plasma ET and increase blood pressure. These changes could be reversed by L-arginine (L-Arg), the substrate of nitric oxide synthase (NOS). The amount of ET released by arterial endothelium could be increased or inhibited by inhibiting or stimulating the synthesis of prostacyclin (PGI2). The plasma ET level and blood pressure in both SHR and WKY rats could be decreased by giving phosphoramidon (PhR). The above results indicate that the biological effects of ET could be antagonized by inhibiting the synthesis or release of ET, decreasing the level of plasma ET, blocking the binding of ET with its receptor and using some Chinese anti-snake venom herb medicines.
Tian
Q
Q
Institute of Cardiovascular Research, Beijing Medical University, China.
Zhao
D
D
Zhang
J
J
Gao
L
L
Liu
S
S
Yang
J
J
Su
J
J
Zhang
Z
Z
Tang
J
J
Tang
C
C
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure; D004365:Drugs, Chinese Herbal / Q000494:pharmacology; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D011464:Epoprostenol / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D008297:Male; D009569:Nitric Oxide / Q000494:pharmacology; D019335:Nitroarginine; D010456:Peptides, Cyclic / Q000494:pharmacology; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017208:Rats, Wistar; D014661:Vasoconstriction
D004365:Drugs, Chinese Herbal; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D006020:Glycopeptides; D010456:Peptides, Cyclic; D011480:Protease Inhibitors; D019335:Nitroarginine; D009569:Nitric Oxide; D001120:Arginine; D011464:Epoprostenol; C072247:cyclo(Trp-Asp-Pro-Val-Leu); C008890:phosphoramidon