Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs
Alterations in cGMP, soluble guanylate cyclase, phosphodiesterase 5, and B-type natriuretic peptide induced by chronic increased pulmonary blood flow in lambs
复制标题
DOI：
10.1002/ppul.20696
复制
发表时间：
2007-11-01
影响因子：
3.1
通讯作者：
Fineman, Jeffrey R.
中科院分区：
文献类型：
--
作者：
Oishi, Peter;Sharma, Shruti;Fineman, Jeffrey R.
目的：本研究的目的是确定cGMP、可溶性鸟苷酸环化酶（sGC）、磷酸二酯酶5型（PDE 5）和B型利钠肽（BNP）在先天性心脏缺陷伴肺血流量增加的动物模型中的变化。设计：前瞻性、比较性、实验性研究。对象：羔羊，从出生到8周龄。方法学：妊娠晚期胎羊在子宫内植入8 mm经皮血管移植物（分流管）。在分流和正常年龄匹配的对照羔羊，在2，4，和8周龄，cGMP和BNP水平进行了测量，sGC亚基和PDE 5蛋白表达的Western印迹分析和免疫组化测定。结果：在8周的研究期间，在分流羔羊中，组织和血浆cGMP水平高于正常（P < 0.05）。sGCa蛋白在2、4周时显著高于对照组（P < 0.05），sGCP和PDE 5蛋白在4周时显著高于对照组（P < 0.05）。正常羔羊血浆BNP水平无明显变化，而转流羔羊血浆BNP水平在8周龄时显著升高（P < 0.05）。术后4周和8周，分流组血浆BNP水平均高于正常组（P < 0.05）。结论：出生后第一个月sGC亚基蛋白表达的改变和出生后第二个月BNP水平的升高导致了肺血流量增加的羔羊血浆和肺组织cGMP升高。
Objective: The objective of the study was to determine alterations in cGMP, soluble guanylate cyclase (sGC), phosphodiesterase type 5 (PDE5), and B-type natriuretic peptide (BNP), in an animal model of a congenital cardiac defect with increased pulmonary blood flow. Design: Prospective, comparative, experimental study. Subjects: Lambs, from birth until 8 weeks of age. Methodology: Late gestation fetal lambs underwent in utero placement of an 8 mm aortopulmonary vascular graft (shunt). In shunted and normal age-matched control lambs, at 2, 4, and 8 weeks of age, cGMP and BNP levels were measured, and sGC subunit and PDE5 protein expression were determined by Western blot analysis and immunchistochemistry. Results: In shunted lambs, tissue and plasma cGMP levels were greater than normal throughout the 8-week study period (P < 0.05). sGCa protein was greater at 2 and 4 weeks (P < 0.05), and sGCP and PDE5 protein were greater at 4 weeks in shunted lambs (P < 0.05). Plasma BNP levels did not change in normal lambs but increased in shunted lambs by 8 weeks of age (P < 0.05). BNP levels were greater in shunted lambs than normal at 4 and 8 weeks (P < 0.05). Conclusions: Alterations in sGC subunit protein expression during the first post-natal month, and increased BNP levels during the second post-natal month contribute to elevations in plasma and lung tissue cGMP in lambs with increased pulmonary blood flow.