Department of Pediatrics, Maastricht University Medical Centre, School for Oncology and Developmental Biology, Maastricht University, Maastricht, the Netherlands.
Am J Physiol Regul Integr Comp Physiol. 2011 Oct;301(4):R1186-98. doi: 10.1152/ajpregu.00729.2010. Epub 2011 Aug 3.
Besides nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H(2)S) is a third gaseous messenger that may play a role in controlling vascular tone and has been proposed to serve as an O(2) sensor. However, whether H(2)S is vasoactive in the ductus arteriosus (DA) has not yet been studied. We investigated, using wire myography, the mechanical responses induced by Na(2)S (1 μM-1 mM), which forms H(2)S and HS(-) in solution, and by authentic CO (0.1 μM-0.1 mM) in DA rings from 19-day chicken embryos. Na(2)S elicited a 100% relaxation (pD(2) 4.02) of 21% O(2)-contracted and a 50.3% relaxation of 62.5 mM KCl-contracted DA rings. Na(2)S-induced relaxation was not affected by presence of the NO synthase inhibitor l-NAME, the soluble guanylate cyclase (sGC) inhibitor ODQ, or the K(+) channel inhibitors tetraethylammonium (TEA; nonselective), 4-aminopyridine (4-AP, K(V)), glibenclamide (K(ATP)), iberiotoxin (BK(Ca)), TRAM-34 (IK(Ca)), and apamin (SK(Ca)). CO also relaxed O(2)-contracted (60.8% relaxation) and KCl-contracted (18.6% relaxation) DA rings. CO-induced relaxation was impaired by ODQ, TEA, and 4-AP (but not by L-NAME, glibenclamide, iberiotoxin, TRAM-34 or apamin), suggesting the involvement of sGC and K(V) channel stimulation. The presence of inhibitors of H(2)S or CO synthesis as well as the H(2)S precursor L-cysteine or the CO precursor hemin did not significantly affect the response of the DA to changes in O(2) tension. Endothelium-dependent and -independent relaxations were also unaffected. In conclusion, our results indicate that the gasotransmitters H(2)S and CO are vasoactive in the chicken DA but they do not suggest an important role for endogenous H(2)S or CO in the control of chicken ductal reactivity.
除了一氧化氮 (NO) 和一氧化碳 (CO) 之外，硫化氢 (H(2)S) 是第三种气态信使分子，可能在控制血管张力方面发挥作用，并被提议作为 O(2) 传感器。然而，H(2)S 是否在动脉导管 (DA) 中具有血管活性尚未得到研究。我们使用线描记法研究了 Na(2)S（1 μM-1 mM）诱导的机械反应，Na(2)S 在溶液中形成 H(2)S 和 HS(-)，以及在 19 天大的鸡胚的 DA 环中诱导的真实 CO（0.1 μM-0.1 mM）。Na(2)S 引起 21% O(2) 收缩的 100%松弛 (pD(2) 4.02) 和 62.5 mM KCl 收缩的 DA 环的 50.3%松弛。Na(2)S 诱导的松弛不受一氧化氮合酶抑制剂 l-NAME、可溶性鸟苷酸环化酶 (sGC) 抑制剂 ODQ 或 K(+) 通道抑制剂四乙铵 (TEA；非选择性)、4-氨基吡啶 (4-AP，K(V))、格列本脲 (K(ATP))、伊比替定 (BK(Ca))、TRAM-34 (IK(Ca)) 和阿帕米 (SK(Ca)) 的影响。CO 也使 O(2) 收缩 (60.8% 松弛) 和 KCl 收缩 (18.6% 松弛) 的 DA 环松弛。CO 诱导的松弛被 ODQ、TEA 和 4-AP 损害（但不受 l-NAME、格列本脲、伊比替定、TRAM-34 或阿帕米的影响），表明 sGC 和 K(V) 通道刺激的参与。H(2)S 或 CO 合成抑制剂的存在以及 H(2)S 前体半胱氨酸或 CO 前体血红素也没有显著影响 DA 对 O(2) 张力变化的反应。内皮依赖性和非依赖性松弛也不受影响。总之，我们的结果表明，气态递质 H(2)S 和 CO 在鸡 DA 中具有血管活性，但它们并不能表明内源性 H(2)S 或 CO 在控制鸡导管反应中具有重要作用。
