Effect of novel potassium channel opener QO-58 on constrictions of human intrrapulmonary arteries ex vivo and its mechanisms

Objective To study the effect of novel potassium channel opener QO-58 on constrictions of human intrrapulmonary arteries ex vivo and its probable mechanisms. Methods Under a microscope in vitro separation of 20 SD rats coronary artery 20 small, 1-1.5 mm in diameter, make every artery vascular ring 10, each 1.8 2.0 mm long, and the following experiments: (1)Each rat only six complete endothelial vascular ring for parallel experiment, add A2 agonists (U46619), high tendency of 60L potassium solution, endothelin 1 (ET1) after processing to produce sustained contraction, the biggest contraction rate of 100%, on the basis of given different concentrations of QO-58 comparison test, divided into the experimental group 1 (10 μmol/L), experiment group 2 (20 μmol/L), experiment 3 groups (50 μmol/L), experiment 4 groups (100 μmol/L), experiment 5 groups (500 μmol/L), and another 1 in vitro small coronary arteries give DMSO as the control group, contrast groups of small artery diastolic level (vascular tension) ring; (2) Take each other rats four endothelial vascular ring, complete shrinkage after processing, take a set of drug concentration of diastolic most obvious experiment concentration, each taking four loop comparison test, group A vascular ring before give QO-58 join L-NAME (eNOS inhibitors) incubation for 30 min, group B will not be processing before using this drug, compared to A, B group of vascular ring vasodilation level; Group C loop in the endothelium, before give QO-58 group D for endothelial vascular ring, complete contrast C, group D vascular ring vasodilatation, explore QO-58 diastolic function mechanism. Results (1)SD rats in vitro small coronary arteries of PD2 (50% relaxation effect vascular tension index), Emax (maximum diastolic rate) are as the first to join QO-increases with the rising of concentration of 58, 50 mu mol/L peak, then gradually reduced, the control loop is no apparent diastolic function, and the PD2 (3.92±0.13)and Emax [ (99.78±0.65)%] for Experiment Group 3 were the highest, diastole effect was most pronounced (F=2.927, P=0.013); (2)Research on mechanism of diastolic, according to the results of PD2, Emax of group A were significantly higher than that of group B (P=0.000); And group C, group D vascular ring PD2, Emax is more difference has no statistical significance (group C vs. group D, PD2: P=0.845, Emax, P=0.715). Conclusion Noble potassium channels open agent (QO-58) in SD rat in vitro small coronary arteries good diastolic function, and the concentration dependence, but excessive concentration of diastolic function weakened, QO-58 without endothelium dependent vasodilatation function mechanism, but QO-58 May help promote the NO release and to expand the role of vascular smooth muscle, improve vascular tension, have clinical application value. Key words: Novel potassium channel opener QO-58; SD rats; Arteries ex vivo; Vascular tension; Mechanisms