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• W2134328477 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 [(±)-(<i>E</i>)-4-ethyl-2-[(<i>E</i>)-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) (≥5 × 10^–3 M) or by tetraethylammonium (>2 × 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 <i>N</i>-[4-[[1-[2-(6-methyl-2-pyridinyl)ethyl]-4-piperidinyl-]carbonyl]phenyl]methanesulfonamide dihydrochloride). Consistent with a role of K_v2-type channels, K_v currents in A7r5 aortic myocytes were stimulated by NTG and inhibited by ≥5 × 10^–3 M 4-AP. Furthermore, immunocytochemistry, immunoblot, and real-time polymerase chain reaction analyses confirmed the presence of K_v2.1 channels in aorta. K_v2.1 transcripts were ∼100-fold more abundant than K_v2.2. Our results support low-affinity 4-AP-sensitive K_v channels, assembled at least partially by K_v2.1 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." @default.
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• W2134328477 date "2006-01-04" @default.
• W2134328477 modified "2023-09-25" @default.
• W2134328477 title "K_vChannels Contribute to Nitric Oxide- and Atrial Natriuretic Peptide-Induced Relaxation of a Rat Conduit Artery" @default.
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• W2134328477 doi "https://doi.org/10.1124/jpet.105.096115" @default.
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