Antagonizing effects of novel multipeptid analogues on endothelin receptors and their pharmacological characteristics in cardiovascular system.
- Author:
Gai-shun FEI
1
;
Li-mei SHAN
;
Shu-hong LIU
;
Yuan-jun LIANG
;
Ke-liang LIU
;
Hai WANG
Author Information
- Publication Type:Journal Article
- MeSH: Animals; Aorta; drug effects; Blood Pressure; drug effects; Endothelin Receptor Antagonists; Endothelins; pharmacology; Hypertension; drug therapy; physiopathology; Male; Molecular Structure; Peptides; chemical synthesis; chemistry; pharmacology; therapeutic use; Rats; Rats, Inbred SHR; Rats, Wistar; Structure-Activity Relationship; Vasoconstriction; drug effects
- From: Acta Pharmaceutica Sinica 2002;37(8):593-597
- CountryChina
- Language:Chinese
-
Abstract:
AIMTo 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.
METHODSOrgan bath experiment and whole cardiac function experiment were used.
RESULTSThe 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.
CONCLUSIONThe results demonstrate that among the six kinds of compounds, those with o-CPhe-D-Trp-D-Phe (-X)-OH configuration showed good biological effects.
