AIM: To evaluate the antagonizing activity of iQWcF, a modified tripeptide, to endothelin receptors. METHODS: 1 Vasoconstriction experiments with aorta strips of rats. 2 In vivo experiments: male normotensive Wistar rats were anesthetized with pentobarbital-Na (50 mg·kg-1), and catheterized into the carotic artery for measurement of blood pressure, and into the femoral vein for administration of iQWcF (30 mg·kg-1) and ET-1(0.9 nmol ·kg-1). The test compound was given intravenously 5 min before the bolus injection of ET-1. Control animals received saline on the same time schedule. The blood pressure was recorded at different time interval after injecting ET-1. RESULTS: 1iQWcF prohibited the vascontriction of aorta induced by ET-1 in a concentration-dependent fashion. 2 The compound (30 mg·kg-1. iv) markedly antagonized ET-1-induced the long-lasting pressor phase mediated by ETA without affecting early transient depressor phase by ETB. CONCLUSION: iQWcF is one of ETA-selective antagonists.

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.

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