[Antagonizing effects of novel multipeptid analogues on endothelin receptors and their pharmacological characteristics in cardiovascular system].
OBJECTIVE
To investigate the antagonistic effects of the novel compounds on vasoconstriction induced by ET-1 and the effect on the blood pressure of stroke-prone spontaneously hypertensive rats.


METHODS
Organ bath experiment and whole cardiac function experiment were used.


RESULTS
The analogues of o-CPhe-D-Trp-D-Phe(-X)-OH showed good ability against endothelin biological effects. When X was displaced by 3-F, 3-Cl or 4-Cl, the novel compounds inhibit the vascular constriction induced by ET-1 in a concentration-dependent manner, the IC50 +/- L95 were (0.09 +/- 0.05), (0.15 +/- 0.06) or (0.11 +/- 0.03) mumol.L-1 respectively. The blood pressure of stroke-prone spontaneously hypertensive rats was decreased. No significant effect on cardiac function of rats was discovered.


CONCLUSIONS
The results demonstrate that among the six kinds of compounds, those with o-CPhe-D-Trp-D-Phe (-X)-OH configuration showed good biological effects.
Fei
Gai-shun
GS
Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China.
Shan
Li-mei
LM
Liu
Shu-hong
SH
Liang
Yuan-jun
YJ
Liu
Ke-liang
KL
Wang
Hai
H
D000818:Animals; D001011:Aorta / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D015394:Molecular Structure; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D013329:Structure-Activity Relationship; D014661:Vasoconstriction / Q000187:drug effects*
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D010455:Peptides