Aim To investigate the effects of iptakalim hydrochl or ide (Ipt), a new antihypertensive drug, on the functions of endothelin system. Methods Radioimmunoassay was used to test the plasma endotheli n (ET) concentration of rats and endothelin released from cultured vasocular end othelial cells. The expressions of ET and endothelin converting enzyme (ECE) wer e determined by RT-PCR. The effects of endothelin on vascular tone were studied in isolated rat aorta. The pulmonary artery pressure was measured in anaestheti zed rats. Results ①In stroke-prone spontaneously hypertensive rats (SHRsp), the plasma levels of endothelin were increased, which could be re versed by the treatment with Ipt at the doses of 0.25,1.0 and 4.0 mg·kg - 1 po, once a day, for 3 months.② In cultured neonatal bovine aortic endotheli al cells (BAEC), Ipt at thc concentrations of 1～1000 μmol·L -1, inhibite d the secretion of ET in a concentra- tion-dependent manner. ③ Under the same experimental conditions, Ip t also inhibited the expressions of ET and ECE in BAEC. ④ In isolated preparati ons derived from rat aorta, the vascular contraction evoked by ET-1 was antagon ized by Ipt at the concentrations of 0.
5～100 μmol·L -1in a concentratio n-dependent manner. The vasorelaxative effects of Ipt were attenuated significa ntly in buffer without Ca 2+. ⑤ In anaesthetized SD rats, intrapulmonary a rtery administration of ET-1 induced vascular contraction in vivo, resulti ng in intrapulmonary artery hypertension, which was prevented by iptakalim hydro chloride at the doses of 0.5～1.0 mg·kg -1. But it had no effects on nor mal pulmonary artery pressure. Conclusion Ipt could antagonize the functions of endothelin system. Its characteristics include inhibiting the e xpression of ET-1 and ECE, inhibiting the releasing of ET-1, reversing the in creased plasma levels of ET-1 under pathological condition, and preventing intr apulmonary artery hypertension induced by ET-1.