Kv channels contribute to nitric oxide- and atrial natriuretic peptide-induced relaxation of a rat conduit artery
Kv channels contribute to nitric oxide- and atrial natriuretic peptide-induced relaxation of a rat conduit artery
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DOI：
10.1124/jpet.105.096115
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发表时间：
2006-04-01
影响因子：
3.5
通讯作者：
Toro, L
中科院分区：
文献类型：
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作者：
Tanaka, Y;Tang, GH;Toro, L
K+ 通道在一氧化氮 (NO) 诱导的血管舒张中的作用已在阻力血管中得到广泛研究，其中伊比利亚毒素敏感的 MaxiK 通道起主要作用。然而，K+ 通道的性质涉及 NO 释放化合物 [ 硝酸甘油、NTG；导管血管主动脉中的NOR 3 [(+/-)-(E)-4-乙基-2-[(E)-羟基亚氨基]-5-硝基-3-己烯酰胺]]或心房钠尿肽(ANP)仍然难以捉摸。我们现在证明，在大鼠主动脉中，这些血管舒张剂引起的松弛不受 MaxiK 通道阻滞剂伊贝里奥毒素 (10(-7) -10(-6) M) 的影响，与所使用的对照血管床（肠系膜动脉）一样。伊比利亚毒素无法阻止 NO/ANP 诱导的主动脉舒张，并不是因为主动脉中 MaxiK 表达较低，也不是因为该导管血管中伊比利亚毒素抗性通道占主导地位。已知可抑制电压依赖性 K+ (K-v) 2 型通道的浓度的 4-氨基吡啶 (4-AP) (>= 5 x 10(-3) M) 或四乙铵 (> 2 x 10(-3) M) 可强烈减弱主动脉松弛，但其他 K+ 通道抑制剂、格列本脲、阿帕明、卡律毒素、特硫平或E-4031 N-[4-[[1-[2-(6-甲基-2-吡啶基)乙基]-4-哌啶基]羰基]苯基]甲磺酰胺二盐酸盐)。与K(v)2 型通道的作用一致，A7r5 主动脉肌细胞中的K-v 电流被NTG 刺激并被>= 5 x 10(-3) M 4-AP 抑制。此外，免疫细胞化学、免疫印迹和实时聚合酶链反应分析证实主动脉中存在 K(v)2.1 通道。 K(v)2.1 转录本的丰度类似于 K(v)2.2 的 100 倍。我们的结果支持低亲和力 4-AP 敏感 K v 通道，至少部分由 K(v)2.1 亚基组装，作为 NO/ANP 信号级联调节主动脉血管舒张的下游效应器，并进一步证明血管特异性 K+ 通道参与 NO/ANP 诱导的舒张。
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) (>= 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 >= 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 similar to 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.