title: Kv channels contribute to nitric oxide- and atrial natriuretic peptide-induced relaxation of a rat conduit artery.
abstract: The role of K(+) channels in nitric oxide (NO)-induced vasorelaxation has been largely investigated in resistance vessels where iberiotoxin-sensitive MaxiK channels play a predominant role. However, the nature of the K(+) channel(s) involved in the relaxation triggered by NO-releasing compounds [nitroglycerin, NTG; NOR 3 [(+/-)-(E)-4-ethyl-2-[(E)-hydroxyimino]-5-nitro-3-hexenamide]] or atrial natriuretic peptide (ANP) in the conduit vessel aorta has remained elusive. We now demonstrate that, in rat aorta, the relaxation due to these vasorelaxants is not affected by the MaxiK channel blocker iberiotoxin (10(-7)-10(-6) M) as was the control vascular bed used (mesenteric artery). The inability of iberiotoxin to prevent NO/ANP-induced aortic relaxations was not due to lower expression of MaxiK in aorta or due to the predominance of iberiotoxin-resistant channels in this conduit vessel. Aortic relaxations were strongly diminished by 4-aminopyridine (4-AP) (> or =5 x 10(-3) M) or by tetraethylammonium (>2 x 10(-3) M) at concentrations known to inhibit voltage-dependent K(+) (K(v)) 2-type channels but not by other K(+) channel inhibitors, glibenclamide, apamin, charybdotoxin, tertiapin, or E-4031 N-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl-]carbonyl]phenyl]methanesulfonamide dihydrochloride). Consistent with a role of K(v)2-type channels, K(v) currents in A7r5 aortic myocytes were stimulated by NTG and inhibited by > or =5 x 10(-3) M 4-AP. Furthermore, immunocytochemistry, immunoblot, and real-time polymerase chain reaction analyses confirmed the presence of K(v)2.1 channels in aorta. K(v)2.1 transcripts were approximately 100-fold more abundant than K(v)2.2. Our results support low-affinity 4-AP-sensitive K(v) channels, assembled at least partially by K(v)2.1 subunit, as downstream effectors of NO/ANP-signaling cascade regulating aortic vasorelaxation and further demonstrate vessel-specific K(+) channel involvement in NO/ANP-induced relaxation.
authors.affiliation: Department of Chemical Pharmacology, Toho University School of Pharmaceutical Sciences, Funabashi-City, Chiba, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Guanghua
authors.initials: G
authors.lastname: Tang
authors.forename: Kei
authors.initials: K
authors.lastname: Takizawa
authors.forename: Kazuoki
authors.initials: K
authors.lastname: Otsuka
authors.forename: Mansoureh
authors.initials: M
authors.lastname: Eghbali
authors.forename: Min
authors.initials: M
authors.lastname: Song
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Nishimaru
authors.forename: Koki
authors.initials: K
authors.lastname: Shigenobu
authors.forename: Katsuo
authors.initials: K
authors.lastname: Koike
authors.forename: Enrico
authors.initials: E
authors.lastname: Stefani
authors.forename: Ligia
authors.initials: L
authors.lastname: Toro
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000378:metabolism / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase; D015151:Immunoblotting; D066298:In Vitro Techniques; D051036:Large-Conductance Calcium-Activated Potassium Channels / Q000096:biosynthesis; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024642:Potassium Channels, Voltage-Gated / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects; D000071756:Soluble Guanylyl Cyclase; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D020030:Nitric Oxide Donors; D026902:Potassium Channel Blockers; D024642:Potassium Channels, Voltage-Gated; D018160:Receptors, Cytoplasmic and Nuclear; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase