ANTAGONIZING EFFECTS OF NOVEL MULTIPEPTID ANALOGUES ON ENDOTHELIN RECEPTORS AND THEIR PHARMACOLOGICALCHARACTERISTICS IN CARDIOVASCULAR SYSTEM

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) μmol·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.