l-Citrulline treatment alters the structure of the pulmonary circulation in hypoxic newborn pigs.
l-Citrulline treatment alters the structure of the pulmonary circulation in hypoxic newborn pigs.
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DOI：
10.1002/ppul.24960
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发表时间：
2020-10
影响因子：
3.1
通讯作者：
Fike CD
中科院分区：
文献类型：
--
作者：
McClellan EB;Wang Z;Albertine KH;Kaplowitz MR;Zhang Y;Fike CD
失调的一氧化氮（NO）信号有助于慢性缺氧（CH）诱导的肺动脉高压（PH）。l -精氨酸-NO前体l -瓜氨酸可改善CH仔猪NO信号传导，降低肺血管阻力（PVR）。我们假设l -瓜氨酸可能会引起肺循环的结构变化，从而导致PVR的降低，并且l -瓜氨酸诱导的结构变化将伴随着VEGF信号的改变。我们评估了从出生日（DOL） 2到DOL 11-12在实验室中饲养的仔猪（10-12% O2）的肺动脉（PA）壁厚、肺毛细血管密度以及PA和外周肺样本中VEGF、VEGFR2和磷酸(p)-VEGFR2的蛋白质丰度，或由供应商在室内空气（常氧）中饲养的仔猪，并在DOL 11-12到达实验室时进行研究。部分CH仔猪在缺氧第3天开始口服l -瓜氨酸（1 ~ 1.5 g/kg/d）。l -瓜氨酸处理的CH仔猪肺壁厚度比未处理的减少32%，肺毛细血管形成几乎增加了一倍。这两种l -瓜氨酸诱导的肺循环结构变化都伴随着VEGF蛋白量的改变，但VEGFR2或p-VEGFR2蛋白的量却没有改变。l -瓜氨酸对CH仔猪肺循环结构的改变不太可能是由整体VEGF信号通路介导的。尽管如此，l -瓜氨酸诱导的结构变化应该会降低PVR，从而有助于改善ch诱导的PH。
Dysregulated nitric oxide (NO) signaling contributes to chronic hypoxia (CH)-induced pulmonary hypertension (PH). NO signaling is improved and pulmonary vascular resistance (PVR) is reduced in CH piglets treated with the L-arginine-NO precursor, L-citrulline. We hypothesized that L-citrulline might cause structural changes in the pulmonary circulation that would contribute to the reduction in PVR and that the L-citrulline-induced structural changes would be accompanied by alterations in VEGF signaling. We evaluated small pulmonary arterial (PA) wall thickness, lung capillary density, and protein abundances of VEGF, VEGFR2, and phospho (p)-VEGFR2 in PA and peripheral lung samples of piglets raised in the lab in CH (10–12% O2) from day of life (DOL) 2 until DOL 11–12 or raised in room air (normoxia) by the vendor and studied on arrival to the lab on DOL 11–12. Some CH piglets were treated with oral L-citrulline (1–1.5 g/kg/d) starting on the third day of hypoxia. PA wall thickness was 32% less and lung capillary formation was nearly doubled in L-citrulline treated than untreated CH piglets. Both of these L-citrulline-induced structural changes in the pulmonary circulation were accompanied by altered amounts of VEGF protein but not by altered amounts of either VEGFR2 or p-VEGFR2 proteins. Alterations in the structure of the pulmonary circulation in CH piglets by L-citrulline are unlikely to be mediated by overall VEGF signaling. Nonetheless, L-citrulline- induced structural changes should reduce PVR and thereby contribute to the amelioration of CH-induced PH.
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影响因子：
3.6
作者：
Nadeau, S;Baribeau, J;Perreault, T
通讯作者：
Perreault, T
影响因子：
4
作者：
dela Paz, Nathaniel G.;Walshe, Tony E.;D'Amore, Patricia A.
通讯作者：
D'Amore, Patricia A.
影响因子：
8.7
作者：
Dulak, J;Józkowicz, A;Cooke, JP
通讯作者：
Cooke, JP
影响因子：
3.3
作者：
FIKE, CD;KAPLOWITZ, MR
通讯作者：
KAPLOWITZ, MR
DOI：
10.1164/rccm.201304-0686pp
发表时间：
2013-09-15
影响因子：
24.7
作者：
Klinger, James R.;Abman, Steven H.;Gladwin, Mark T.
通讯作者：
Gladwin, Mark T.