Mechanisms of relaxing response induced by rat/mouse hemokinin-1 in porcine coronary arteries: Roles of potassium ion and nitric oxide

Rat and mouse hemokinin-1(r/m hemokinin-1) is a recently described member of the tachykinin family whose cardiovascular functions are not fully understood. In this study, we investigated the mechanisms of the relaxing response induced by r/m hemokinin-1 in isolated porcine coronary arteries by using a specific antagonist of tachykinin NK1 receptor (SR140333), a nitric oxide synthase inhibitor Nω-nitro-l-arginine (l-NNA), and 1H-[1,2,4] Oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), a blocker of cGMP production. r/m Hemokinin-1 (10− 12–10− 6 M) evoked a marked endothelium-dependent vasodilatation (Emax = 121.12 ± 10.6% and 91.79 ± 2.39% in 10− 6 M PGF2α and 30 mM KCl precontracted arterial rings, respectively) of coronary arteries mediated by activation of endothelial tachykinin NK1 receptors. Two components contributed to this r/m hemokinin-1-elicited vasodilatation, the first of which was endothelium-derived hyperpolarizing factor (EDHF), which played a major role. This EDHF was identified as a potassium current through certain kinds of potassium channels on the endothelial cell membrane of porcine coronary arteries. Specific antagonists of Ca2+-activated K+ channels (dequalinium and clotrimazole) did not have an inhibitory effect on the r/m hemokinin-1-induced vasodilatation, whereas they did on the substance P-induced vasodilatation. When potassium ion efflux was impaired by a high K+ concentration (30 mM) or removal of K+ from the surroundings, NO synthesis was triggered by r/m hemokinin-1 to produce an equivalent EDHF (K+)-independent vasorelaxation as a compensatory mechanism.