Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries.
Hypoxia enhances a cGMP-independent nitric oxide relaxing mechanism in pulmonary arteries.
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缺氧增强了肺动脉中不依赖 cGMP 的一氧化氮舒张机制。
DOI：
10.1152/ajplung.00362.2002
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
Wolin,MichaelS
中科院分区：
文献类型：
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作者：
Mingone,ChristopherJ;Gupte,SachinA;Iesaki,Takafumi;Wolin,MichaelS
一氧化氮（NO）供体通常通过cGMP介导的机制使血管制剂松弛。用10 μM 1H-[1，2，4]恶二唑并[4，3-a]喹喔啉-1-酮（ODQ）抑制可溶性鸟苷酸环化酶的活化，几乎消除了去内皮牛肺动脉（BPA）和冠状动脉对NO供体S-亚硝基-N-乙酰青霉胺（SNAP）的舒张作用，而在缺氧（PO 2 = 8-10 Torr）条件下，仅观察到适度的舒张抑制作用。缺氧的这种作用与所用的收缩剂无关，并且在NO气体的情况下也观察到。ODQ消除了BPA缺氧条件下SNAP诱导的cGMP增加。抑制K+通道（10 mM四乙铵）、肌球蛋白轻链磷酸酶（0.5 μM微囊藻毒素-LR）或腺苷酸环化酶（4 μM 2′，5 ′-二脱氧腺苷）不会减弱BPA对SNAP的cGMP非依赖性舒张。SNAP松弛BPA收缩与血清素在无钙条件下，在缺氧和ODQ的存在下，和收缩到Ca 2 +readdition也减弱。肌浆网钙再摄取抑制剂cyclopiazonic酸（0.2毫米）衰减SNAP介导的松弛BPA在ODQ的存在下。因此，缺氧条件下出现促进cGMP-独立的放松BPA NO通过增强肌浆网Ca 2+再摄取。
Nitric oxide (NO) donors generally relax vascular preparations through cGMP-mediated mechanisms. Relaxation of endothelium-denuded bovine pulmonary arteries (BPA) and coronary arteries to the NO donorS-nitroso-N-acetyl-penicillamine (SNAP) is almost eliminated by inhibition of soluble guanylate cyclase activation with 10 μM 1H-[1,2,4]oxadiazolo-[4,3-a]quinoxalin-1-one (ODQ), whereas only a modest inhibition of relaxation is observed under hypoxia (PO2= 8–10 Torr). This effect of hypoxia is independent of the contractile agent used and is also observed with NO gas. ODQ eliminated SNAP-induced increases in cGMP under hypoxia in BPA. cGMP-independent relaxation of BPA to SNAP was not attenuated by inhibition of K+channels (10 mM tetraethylammonium), myosin light chain phosphatase (0.5 μM microcystin-LR), or adenylate cyclase (4 μM 2′,5′-dideoxyadenosine). SNAP relaxed BPA contracted with serotonin under Ca2+-free conditions in the presence of hypoxia and ODQ, and contraction to Ca2+readdition was also attenuated. The sarcoplasmic reticulum Ca2+-reuptake inhibitor cyclopiazonic acid (0.2 mM) attenuated SNAP-mediated relaxation of BPA in the presence of ODQ. Thus hypoxic conditions appear to promote a cGMP-independent relaxation of BPA to NO by enhancing sarcoplasmic reticulum Ca2+reuptake.