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首页> 外文期刊>American Journal of Physiology >sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension.
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sGC and PDE5 are elevated in lambs with increased pulmonary blood flow and pulmonary hypertension.

机译：羔羊的sGC和PDE5升高，肺血流量增加和肺动脉高压增加。

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Utilizing aortopulmonary vascular graft placement, we established a lamb model of pulmonary hypertension that mimics congenital heart disease with increased pulmonary blood flow. We previously demonstrated that endothelial nitric oxide synthase (eNOS) is increased in lambs at age 4 wk. However, these lambs display a selective impairment of endothelium-dependent pulmonary vasodilation that is suggestive of a derangement downstream of NO release. Thus our objective was to characterize potential alterations in the expression and activity of soluble guanylate cyclase (sGC) and phosphodiesterase type 5 (PDE5) induced by increased pulmonary blood flow and pulmonary hypertension. Late-gestational fetal lambs (n = 10) underwent in utero placement of an aortopulmonary vascular graft (shunt). Western blotting analysis on lung tissue from 4-wk-old shunted lambs and age-matched controls showed that protein for both subunits of sGC was increased in shunted lamb lungs compared with age-matched controls. Similarly, cGMP levels were increased in shunted lamb lungs compared with age-matched controls. However, PDE5 expression and activity were also increased in shunted lambs. Thus although cGMP generation was increased, concomitant upregulation of PDE5 expression and activity may have (at least partially) limited and accounted for the impairment of endothelium-dependent pulmonary vasodilation in shunted lambs.
机译：利用主肺血管移植物放置，我们建立了肺动脉高压的羔羊模型，该模型模拟了先天性心脏病并增加了肺血流量。先前我们证明了4周龄羔羊的内皮一氧化氮合酶（eNOS）增加。然而，这些羔羊表现出对内皮依赖性肺血管舒张的选择性损伤，这提示NO释放下游的紊乱。因此，我们的目标是表征由于肺血流量增加和肺动脉高压引起的可溶性鸟苷酸环化酶（sGC）和5型磷酸二酯酶（PDE5）的表达和活性的潜在变化。晚期胎羊（n = 10）在子​​宫内放置主肺血管移植物（分流）。对来自4周龄分流羔羊和年龄匹配的对照组肺组织的蛋白质印迹分析表明，与年龄匹配的对照组相比，分流的羔羊肺中sGC的两个亚基的蛋白质均增加。同样，与年龄匹配的对照组相比，分流的羔羊肺中的cGMP水平升高。但是，PDE5的表达和活性在分流羔羊中也增加。因此，尽管增加了cGMP生成，但PDE5表达和活性的同时上调可能（至少部分）受到限制，并解释了分流羔羊内皮依赖性肺血管舒张功能的损害。

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