Vasodilation effect of nitrate FLNT on the porcine coronary artery and its mechanism

Objective:To investigate the vasodilation effect on the porcine coronary artery and the possible mechanism of nitrate FLNT.Methods: The tension of porcine coronary artery precontracted with potassium chloride(KCl,30 mmol·L-1),histamine(His,10-3 mmol·L-1),or acetylcholine(ACh,10-3 mmol·L-1) was measured.The vasodilation effect of FLNT was compared to that of nitroglycerin(NG) or isosorbide dinitrate(ISDN).Mythelene blue,the blocker of guanylate cyclase(GC), and the specific blockers of inward rectifier potassium channel,Ca2+ activated potassium channel,voltage-dependent potassium channel and ATP-sensitive potassium channel(BaCl2,tetraethylammonium,4-aminopyridine,glibenclamide) were used,respectively,to clarify the mechanism of FLNT vasodilation.Results: In porcine coronary artery rings precontracted with KCl,His or ACh,FLNT(10-4～10-1 mmol·L-1) caused the concentration-dependent relaxation in both the endothelium intact and denuded arterial rings.FLNT relaxation was almost the same as ISDN.FLNT shifted KCl concentration-response curve to the right and decreased the maximum response with a pD′2 of 3.68.Mythelene blue reduced FLNT vasodilatin.FLNT,like nicorandil,reduced the vessel tension precontracted with some potassium channel blockers.Conclusion: FLNT endothelium-independently and concentration-dependently induces relaxation of porcine coronary artery,which is similar to isosorbide dinitrate.The mechanism may relate to guanylate cyclase activation,potassium channel opening,and the inhibition of voltage-dependent Ca2+ channel and receptor-controlled Ca2+ channel.