Kun Attila, Martinez Ana Cristina, Tankó László B, Pataricza János, Papp Julius Gy, Simonsen Ulf
Department of Pharmacology, University of Aarhus, 8000 Aarhus C, Denmark.
Eur J Pharmacol. 2003 Aug 1;474(1):103-15. doi: 10.1016/s0014-2999(03)02004-1.
The present study was designed to investigate the functional K+ channels involved in contractions induced by electrical field stimulation in isolated rat penile arteries. Blockers of Ca2+-activated K+ channels (KCa), tetraethylammonium, and of large-conductance KCa channels, charybdotoxin and iberiotoxin, as well as a blocker of voltage-dependent K+ channels (KV), 4-aminopyridine, increased resting tension in penile small arteries. In the presence of propranolol and NG-nitro-L-arginine (L-NOARG), electrical field stimulation evoked prazosin-sensitive contractions. In endothelium-intact preparations, these latter contractions were enhanced in the presence of tetraethylammonium and charybdotoxin. However, these blockers did not enhance contractions evoked by exogenously added noradrenaline. Endothelial cell removal increased the neurogenic contractions but tetraethylammonium had no further potentiating effect in these preparations. In the presence of an inhibitor of cyclooxygenase, indomethacin, and inhibitor of nitric oxide (NO) synthase, L-NOARG, acetylcholine evoked relaxations, which were abolished in the presence of either tetraethylammonium or charybdotoxin. In phenylephrine-contracted arteries treated with guanethidine and atropine, electrical field stimulation evoked relaxations, which were partially inhibited by L-NOARG and tetraethylammonium, without any additive effect of these drugs. These observations suggest that both large-conductance KCa channels and KV channels sensitive to iberiotoxin/tetraethylammonium and 4-aminopyridine, respectively, are directly involved in the modulation of myogenic tone of rat penile arteries. Furthermore, activation of endothelial intermediate-conductance KCa channels sensitive to tetraethylammonium and charybdotoxin leads to release of a non-NO nonprostanoid factor, which inhibits release of the neurotransmitter, noradrenaline, but these channels do not appear to be involved in inhibition of contraction evoked by exogenously applied noradrenaline in rat penile arteries.
本研究旨在探究参与电场刺激诱导的离体大鼠阴茎动脉收缩的功能性钾通道。钙激活钾通道（KCa）阻滞剂四乙铵、大电导KCa通道阻滞剂蝎毒素和蜂毒明肽，以及电压依赖性钾通道（KV）阻滞剂4-氨基吡啶，均可增加阴茎小动脉的静息张力。在普萘洛尔和NG-硝基-L-精氨酸（L-NOARG）存在的情况下，电场刺激可诱发对哌唑嗪敏感的收缩。在内皮完整的标本中，在四乙铵和蝎毒素存在的情况下，后一种收缩增强。然而，这些阻滞剂并未增强外源性添加去甲肾上腺素所诱发的收缩。去除内皮细胞可增加神经源性收缩，但四乙铵在这些标本中没有进一步的增强作用。在存在环氧化酶抑制剂吲哚美辛和一氧化氮（NO）合酶抑制剂L-NOARG的情况下，乙酰胆碱可诱发舒张，而在四乙铵或蝎毒素存在时，这种舒张被消除。在用胍乙啶和阿托品处理的去氧肾上腺素收缩的动脉中，电场刺激可诱发舒张，L-NOARG和四乙铵可部分抑制这种舒张，且这些药物没有任何相加作用。这些观察结果表明，分别对蜂毒明肽/四乙铵和4-氨基吡啶敏感的大电导KCa通道和KV通道直接参与了大鼠阴茎动脉肌源性张力的调节。此外，对四乙铵和蝎毒素敏感的内皮中电导KCa通道的激活导致一种非NO非前列腺素因子的释放，该因子抑制神经递质去甲肾上腺素的释放，但这些通道似乎不参与抑制外源性应用去甲肾上腺素在大鼠阴茎动脉中诱发的收缩。
