Low guanylyl cyclase activity in Weddell seals: implications for peripheral vasoconstriction and perfusion of the brain during diving
Low guanylyl cyclase activity in Weddell seals: implications for peripheral vasoconstriction and perfusion of the brain during diving
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DOI：
10.1152/ajpregu.00283.2018
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发表时间：
2019-06-01
影响因子：
2.8
通讯作者：
Buys, Emmanuel S.
中科院分区：
文献类型：
--
作者：
Hindle, Allyson G.;Allen, Kaitlin N.;Buys, Emmanuel S.
一氧化氮（NO）是一种强有力的血管扩张剂，在陆生动物组织缺氧时可改善灌注和氧输送。脊椎动物的潜水反应涉及选择组织中的血管收缩。尽管严重缺氧但仍持续存在。使用从威德尔海豹尸检收集的组织，我们研究了是否血管收缩是通过下调局部缺氧信号传导机制的帮助。我们专注于NO可溶性鸟苷酸环化酶（GC）-cGMP信号，一个众所周知的血管舒张转导途径。海豹的GC蛋白丰度较低。活性和对NO刺激的反应能力。在海豹肺匀浆中，GC产生的cGMP（20.1 +/- 3.7 pmol.mg protein（-1）.min（-1））低于犬肺（比海豹少-80 +/- 144 pmol.mg protein（-1）.min（-1））、绵羊肺（-472 +/- 96）、大鼠肺（-664 +/- 104）或小鼠肺（-1，160 +/- 104，P < 0.0001）。GC酶α亚基的氨基酸序列在海豹和陆地哺乳动物之间存在差异，可能影响它们的结构和功能。潜水威德尔海豹的血管收缩在各组织中并不一致;大脑和心脏的灌注保持不变，但其他器官如肾脏的灌注减少。NO供体使海豹脑中的GC活性中值增加49.5倍，但在肾脏中仅增加27.4倍。符合潜水时脑灌注的优先顺序。NOS 3在脑组织中高表达，可促进NO的产生和血管舒张功能。相反，Pde 5a在海豹肾动脉中表达高，这可能增加肾脏中的cGMP分解和血管收缩。总之，本研究的结果表明，NO-cGMP途径的改变促进了潜水反应。
Nitric oxide (NO) is a potent vasodilator, which improves perfusion and oxygen delivery during tissue hypoxia in terrestrial animals. The vertebrate dive response involves vasoconstriction in select tissues. which persists despite profound hypoxia. Using tissues collected from Weddell seals at necropsy, we investigated whether vasoconstriction is aided by downregulation of local hypoxia signaling mechanisms. We focused on NO-soluble guanylyl cyclasc (GC)-cGMP signaling, a well-known vasodilatory transduction pathway. Seals have a lower GC protein abundance. activity, and capacity to respond to NO stimulation than do terrestrial mammals. In seal lung homogenates, GC produced less cGMP (20.1 +/- 3.7 pmol.mg protein(-1).min(-1)) than the lungs of dogs (-80 +/- 144 pmol.mg protein(-1).min(-1) less than seals), sheep (-472 +/- 96), rats (-664 +/- 104) or mice ( -1,160 +/- 104, P < 0.0001). Amino acid sequences of the GC enzyme alpha-subunits differed between seals and terrestrial mammals, potentially affecting their structure and function. Vasoconstriction in diving Weddell seals is not consistent across tissues; perfusion is maintained in the brain and heart but decreased in other organs such as the kidney. A NO donor increased median GC activity 49.5-fold in the seal brain but only 27.4-fold in the kidney. consistent with the priority of cerebral perfusion during diving. Nos3 expression was high in the seal brain, which could improve NO production and vasodilatory potential. Conversely, Pde5a expression was high in the seal renal artery, which may increase cGMP breakdown and vasoconstriction in the kidney. Taken together, the results of this study suggest that alterations in the NO-cGMP pathway facilitate the diving response.