title: Mechanisms of relaxing response induced by rat/mouse hemokinin-1 in porcine coronary arteries: roles of potassium ion and nitric oxide.
abstract: 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 NK(1) receptor (SR140333), a nitric oxide synthase inhibitor N(omega)-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 (E(max)=121.12+/-10.6% and 91.79+/-2.39% in 10(-6) M PGF(2)alpha and 30 mM KCl precontracted arterial rings, respectively) of coronary arteries mediated by activation of endothelial tachykinin NK(1) 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 Ca(2+)-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.
authors.affiliation: Key Laboratory of Preclinical Study for New Drugs of Gansu Province, Institute of Biochemistry and Molecular Biology, Lanzhou University, 222 Tianshui South Road, Lanzhou, 730000, PR China.
authors.forename: Yuan
authors.initials: Y
authors.lastname: Long
authors.forename: Cai-Yun
authors.initials: CY
authors.lastname: Fu
authors.forename: Xiao-Zhu
authors.initials: XZ
authors.lastname: Tian
authors.forename: Juan
authors.initials: J
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Han
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
mesh_terms: D000818:Animals; D000891:Anti-Infective Agents, Local / Q000494:pharmacology; D003022:Clotrimazole / Q000494:pharmacology; D003331:Coronary Vessels / Q000187:drug effects* / Q000502:physiology; D003868:Dequalinium / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D051379:Mice; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D019335:Nitroarginine / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011498:Protein Precursors / Q000494:pharmacology*; D011810:Quinoxalines / Q000494:pharmacology; D011812:Quinuclidines / Q000494:pharmacology; D051381:Rats; D018040:Receptors, Neurokinin-1 / Q000502:physiology; D011982:Receptors, Prostaglandin / Q000502:physiology; D013373:Substance P / Q000037:antagonists & inhibitors / Q000494:pharmacology; D013552:Swine; D015320:Tachykinins / Q000494:pharmacology*; D019789:Tetraethylammonium / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects* / Q000502:physiology
chemical_list: C095284:1H-(1,2,4)oxadiazolo(4,3-a)quinoxalin-1-one; D000891:Anti-Infective Agents, Local; D004791:Enzyme Inhibitors; D064729:Neurokinin-1 Receptor Antagonists; D018377:Neurotransmitter Agents; D010069:Oxadiazoles; D010880:Piperidines; D026902:Potassium Channel Blockers; D011498:Protein Precursors; D011810:Quinoxalines; D011812:Quinuclidines; D018040:Receptors, Neurokinin-1; D011982:Receptors, Prostaglandin; C423233:Tac4 protein, mouse; D015320:Tachykinins; C034671:prostaglandin F2alpha receptor; C085215:SR 140333; D019335:Nitroarginine; D009569:Nitric Oxide; D013373:Substance P; D019789:Tetraethylammonium; D003868:Dequalinium; D003022:Clotrimazole; D011188:Potassium