Aim To investigate the vasodilatory mechanisms of C-type natriuretic peptide(CNP) via the natriuretic peptide receptor-C(NPR-C) pathway.Methods This study was performed on the porcine coronary artery rings,and the tension changes of coronary artery ring were recorded with the presence of CNP or NPR-C agonist(cANF4-23),further NPR-C antagonist(cANF4-28),Gi protein blocker(pertussis toxin,PTx) and four types of potassium channel blocker were used to explore the vasodilatory mechanisms.Results Vasorelaxant activities to 10-6mol/L CNP and cANF4-23 were 36.51%±3.96% and 42.37%±17.60% respectively(P>0.05);cANF4-28 or PTx can attenuate the action of both CNP and cANF4-23(P<0.05);Tetraethylammonium,Glibenclamide or BaCl2 all can attenuate the relaxant activity of CNP(P<0.05),but only BaCl2 decreased the vasodilatory action of cANF4-23(P<0.05).Conclusions Activation of the G protein-coupled inwardly-rectifying potassium channel(GIRK) maybe account for the vasodilatory action of CNP via the NPR-C pathway.