Olson Kenneth R, Dombkowski Ryan A, Russell Michael J, Doellman Meredith M, Head Sally K, Whitfield Nathan L, Madden Jane A
Indiana University School of Medicine-South Bend, 1234 Notre Dame Avenue, South Bend, IN 46617, USA.
J Exp Biol. 2006 Oct;209(Pt 20):4011-23. doi: 10.1242/jeb.02480.
How vertebrate blood vessels sense acute hypoxia and respond either by constricting (hypoxic vasoconstriction) or dilating (hypoxic vasodilation) has not been resolved. In the present study we compared the mechanical and electrical responses of select blood vessels to hypoxia and H2S, measured vascular H2S production, and evaluated the effects of inhibitors of H2S synthesis and addition of the H2S precursor, cysteine, on hypoxic vasoconstriction and hypoxic vasodilation. We found that: (1) in all vertebrate vessels examined to date, hypoxia and H2S produce temporally and quantitatively identical responses even though the responses vary from constriction (lamprey dorsal aorta; lDA), to dilation (rat aorta; rA), to multi-phasic (rat and bovine pulmonary arteries; rPA and bPA, respectively). (2) The responses of lDA, rA and bPA to hypoxia and H2S appear competitive; in the presence of one stimulus, the response to the other stimulus is substantially or completely eliminated. (3) Hypoxia and H2S produce the same degree of cell depolarization in bPA. (4) H2S is constitutively synthesized by lDA and bPA vascular smooth muscle. (5) Inhibition of H2S synthesis inhibits the hypoxic response of lDA, rA, rPA and bPA. (6) Addition of the H2S precursor, cysteine, doubles hypoxic contraction in lDA, prolongs contraction in bPA and alters the re-oxygenation response of rA. These studies suggest that H2S may serve as an O2 sensor/transducer in the vascular responses to hypoxia. In this model, the concentration of vasoactive H2S in the vessel is governed by the balance between endogenous H2S production and its oxidation by available O2.
脊椎动物血管如何感知急性缺氧并通过收缩（缺氧性血管收缩）或扩张（缺氧性血管舒张）做出反应尚未得到解决。在本研究中，我们比较了特定血管对缺氧和硫化氢的机械和电反应，测量了血管硫化氢的产生，并评估了硫化氢合成抑制剂以及添加硫化氢前体半胱氨酸对缺氧性血管收缩和缺氧性血管舒张的影响。我们发现：（1）在迄今为止检查的所有脊椎动物血管中，缺氧和硫化氢产生的时间和定量反应相同，尽管反应有所不同，从收缩（七鳃鳗背主动脉；lDA）到扩张（大鼠主动脉；rA），再到多相反应（大鼠和牛肺动脉；分别为rPA和bPA）。（2）lDA、rA和bPA对缺氧和硫化氢的反应似乎具有竞争性；在存在一种刺激的情况下，对另一种刺激的反应会大幅或完全消除。（3）缺氧和硫化氢在bPA中产生相同程度的细胞去极化。（4）lDA和bPA血管平滑肌可组成性合成硫化氢。（5）抑制硫化氢合成会抑制lDA、rA、rPA和bPA的缺氧反应。（6）添加硫化氢前体半胱氨酸会使lDA中的缺氧收缩加倍，延长bPA中的收缩时间，并改变rA的复氧反应。这些研究表明，硫化氢可能在血管对缺氧的反应中充当氧传感器/转导器。在这个模型中，血管中血管活性硫化氢的浓度由内源性硫化氢产生与其被可用氧气氧化之间的平衡所控制。
