Nitric oxide sensitivity in pulmonary artery and airway smooth muscle: a possible role for cGMP responsiveness.
Nitric oxide sensitivity in pulmonary artery and airway smooth muscle: a possible role for cGMP responsiveness.
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肺动脉和气道平滑肌中的一氧化氮敏感性：cGMP 反应性的可能作用。
DOI：
10.1152/ajplung.00402.2005
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Perkins,WilliamJ
中科院分区：
文献类型：
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作者：
Taniguchi,Miwa;Kwak,YoungLan;Jones,KeithA;Warner,DavidO;Perkins,WilliamJ
我们的目的是评估内在的平滑肌机制，有助于更大的一氧化氮（NO）反应性肺血管与气道平滑肌。应用猪肺动脉平滑肌（PASM）和气管平滑肌（TSM）条研究NO供体（Z）-1-[N-2-氨乙基-N-（2-ammonioethyl）amino]diazen-1-鎓-1，2-diolate（Z-NO）的浓度-反应。PASM在给定的α-NO浓度下（NO反应性）始终表现出比TSM NO反应性更大的舒张作用，PASM和TSM的α-NO log EC 50分别为−6.55 ± 0.11和−5.37 ± 0.13（P< 0.01）。我们使用鸟苷酸环化酶激动剂心房利钠肽测定了组织cGMP浓度（[cGMP]i）和舒张之间的关系。心房利钠肽导致几乎完全的舒张，在PASM中没有检测到[cGMP] i的增加，而在TSM中只有20%的舒张（[cGMP]i增加10倍），表明TSM的cGMP响应性低于PASM。PASM中总cGMP依赖性蛋白激酶I（cGKI）mRNA表达高于TSM（分别为2.23 ± 0.36和0.93 ± 0.31阿莫尔mRNA/μg总RNA;P< 0.01），但总cGKI蛋白表达无显著差异（分别为0.56 ± 0.07和0.49 ± 0.04 ng cGKI/μg蛋白）。组织匀浆可溶性部分的磷酸转移酶测定表明PASM和TSM之间的cGMP EC 50无差异。PASM和TSM之间以匀浆中总cGKI量为指标的最大磷酸转移酶活性存在显著差异（分别为1.61 ± 0.15和1.04 ± pmol·min-1·ng cGKI-1;P< 0.05），表明cGKI在两种组织中的调节可能不同。因此，一种新的内在平滑肌机制解释了PASM相对于TSM中更大的NO反应性，即PASM中cGMP特异性活性增加导致cGMP反应性更大。
We aimed to assess intrinsic smooth muscle mechanisms contributing to greater nitric oxide (NO) responsiveness in pulmonary vascular vs. airway smooth muscle. Porcine pulmonary artery smooth muscle (PASM) and tracheal smooth muscle (TSM) strips were used in concentration-response studies to the NO donor (Z)-1-[N-2-aminoethyl-N-(2-ammonioethyl)amino]diazen-1-ium-1,2-diolate (DETA-NO). PASM consistently exhibited greater relaxation at a given DETA-NO concentration (NO responsiveness) than TSM NO responsiveness, with DETA-NO log EC50being −6.55 ± 0.11 and −5.37 ± 0.13 for PASM and TSM, respectively (P< 0.01). We determined relationships between tissue cGMP concentration ([cGMP]i) and relaxation using the particulate guanylyl cyclase agonist atrial natriuretic peptide. Atrial natriuretic peptide resulted in nearly complete relaxation, with no detectable increase in [cGMP]iin PASM and only 20% relaxation (10-fold increase in [cGMP]i) in TSM, indicating that TSM is less cGMP responsive than PASM. Total cGMP-dependent protein kinase I (cGKI) mRNA expression was greater in PASM than in TSM (2.23 ± 0.36 vs. 0.93 ± 0.31 amol mRNA/μg total RNA, respectively;P< 0.01), but total cGKI protein expression was not significantly different (0.56 ± 0.07 and 0.49 ± 0.04 ng cGKI/μg protein, respectively). The phosphotransferase assay for the soluble fraction of tissue homogenates demonstrated no difference in the cGMP EC50between PASM and TSM. The maximal phosphotransferase activity indexed to the amount of total cGKI in the homogenate differed significantly between PASM and TSM (1.61 ± 0.15 and 1.04 ± pmol·min−1·ng cGKI−1, respectively;P< 0.05), suggesting that cGKI may be regulated differently in the two tissues. A novel intrinsic smooth muscle mechanism accounting for greater NO responsiveness in PASM vs. TSM is thus greater cGMP responsiveness from increased cGKI-specific activity in PASM.