Effects Of Iptakalim On The Isolated Human Pulmonary Artery Constriction Induced By ET-1

Objective To investigate the vasodilativemechanism and effects of iptakalim (IPT), a novel K_ATPchannel opener, on the constriction of isolated humanpulmonary artery induced by endothelin-1.Pulmonary arteryhypertension is an very important secondarypathophysiologic process of chronic heart disease,chronicobstructive pulmonary disease and other hypoxic disease.With the growing understanding of the pulmonary vascularremodeling, the therapy target of PAH has been changedfrom vasodilators to ion channels in the cells.Methods The effects of IPT administered by cumulativemethod on vasoconstriction mediated by ET-1 were studiedwith rings of pulmonary artery isolated from the lungs whichwas collected after the lobectomy of thirty-eight patientswith lung tumor. Vascular tensions were recorded under cumulative concentration of NS, IPT and pinacidil (PIN).After the PASMC were baded with the Fluo-3/AM,[Ca²⁺_I was measured by Laser Scanning ConfocalMicroscopy (LSCM). It was used to study the change of[Ca²⁺]_I in PASMC treated by ET-1 and IPT.Results In the studies, at the concentration of 0.05～50nmol/L, ET-1 induced a significant increase of vasculartension in concentration-dependent manner, the EC₅₀±L₉₅was 10.19±1.26nmol/L, b±S_b was 0.905±0.186, r=0.91.And IPT at the concentration of 10^-13～10^-3 mol/L,antagonized vasoconstriction induced by ET-1 inconcentration-dependent manner, IC₅₀ was 27.11nmol/L,There is no significant difference between the effects causedby IPT and PIN (P＜0.05). Observed by the LSCM in every 5seconds, ET-1 stimulate the cells can sharply increased the[Ca²⁺]_I of PASMC, and IPT can decreased it.Conclusion Comparing with the result of animalexperiments, ET-1, at concentration of 10nmol/L,significantly induced the constriction effect of humanpulmonary artery, and the time and tension of this effect ismuch increased. IPT can significantly antagonize thevasoconstriction induced by ET-1, through activating the K_ATP channel in the pulmonary artery without affecting thenormal pulmonary artery pressure。ET-1 sharply increasedthe [Ca²⁺]_I of the PASMC, but IPT decreased it. Weconsider that IPT is an ideal candidate medicine forpulmonary artery hypertension therapy.