RESUMO
AIM To determine the antagonistic activities of new endothelin receptor antagonist CPU0214 on the left ventricle membranes and the aorta ring contraction in normal rat and its reduction effect on the mean arterial pressure in conscious DOCA salt hypertensive rats. METHODS Left ventricle membranes of normal rat hearts achieved for competition binding assay was used to investigate the antagonistic effects of CPU0214. Aorta ring contraction induced by ET 1 in normal rat was used to investigate the antagonistic activity of CPU0214. DOCA salt hypertensive rats were induced by injection of deoxycorticosterone acetate (DOCA, sc) following with 1% NaCl as drinking for 4 wk. A multiple physiological recorder was used to record the mean arterial pressure of femoral artery. The endothelin receptor change in the left ventricle membranes of DOCA salt hypertensive rat was measured by binding assays. Intraperitoneal injection of CPU0214 was used to investigate its effect on reduction of mean arterial pressure. RESULTS In the left ventricle the IC 50 of endothelin receptor antagonist CPU0214 is 16 nmol?L -1 and CPU0214 (10 ?mol?L -1 ) inhibited the ET 1 induced isolated aorta rings contraction in normal rats. Mean arterial pressure as well as B max and K d of left ventricle were increased significantly in DOCA salt hypertensive rat. CPU0214 (60 mg?kg -1 ip) significantly reduced the mean arterial pressure of conscious DOCA salt hypertensive rats especially during 60～90 min after administration. CONCLUSIONS CPU0214 has significantly antagonistic effects on the left ventricle membrane and the isolated aorta ring contraction in normal rat, which is verified by CPU0214 as a strong endothelin receptor antagonist. Furthermore its effect on the mean blood pressure reduction in conscious DOCA salt hypertensive rats, which is manifested as an abnormal endothelin system, shows its prosperity of drug development value as a new endothelin receptor antagonist.