C-type natriuretic peptide does not attenuate the development of pulmonary hypertension caused by hypoxia and VEGF receptor blockade
C-type natriuretic peptide does not attenuate the development of pulmonary hypertension caused by hypoxia and VEGF receptor blockade
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DOI：
10.1016/j.lfs.2011.07.009
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发表时间：
2011-09-26
期刊：
影响因子：
6.1
通讯作者：
Choudhary, Gaurav
中科院分区：
文献类型：
--
作者：
Casserly, Brian;Mazer, Jeffrey M.;Choudhary, Gaurav
目的：C型利钠肽(CNP)是许多血管床血管张力和重塑的局部调节因子。然而，CNP在调节肺动脉高压和血管重塑反应中的作用尚不清楚。本研究的目的是确定CNP是否能够预防肺动脉高压(PH)的发展。主要方法：采用单独或联合血管内皮生长因子(VEGF)受体阻滞剂SU5416建立慢性低氧所致PH的动物模型。我们测量了持续输注低剂量或高剂量CNP或安慰剂对肺血流动力学、右室肥厚和血管重构的影响。关键发现：两种PH模型均可见右室肥厚和右室收缩压(RVSP)显著升高。接受SU5416和慢性低氧联合治疗的大鼠也出现了肺内皮细胞的过度增殖损伤。持续静脉滴注两种剂量的CNP均不能抑制PH的发展、右室肥厚或血管重构，尽管血清CNP水平增加了三倍。意义：在慢性低氧或SU5416加低氧的肺动脉高压模型中，CNP不能阻止PH的发生，提示CNP在人的PH中可能不起重要的调节作用。由爱思唯尔公司出版。
Aims: C-type natriuretic peptide (CNP) is a local regulator of vascular tone and remodeling in many vascular beds. However, the role of CNP in modulating pulmonary arterial hypertensive and vascular remodeling responses is unclear. The purpose of this study was to determine if CNP is capable of preventing the development of pulmonary hypertension (PH).Main methods: We used animal models of PH caused by chronic hypoxia alone or in combination with the vascular endothelial growth factor (VEGF) receptor blocker SU5416. We measured pulmonary hemodynamics, right ventricular hypertrophy and vascular remodeling effects in response to a continuous infusion of low dose or high dose CNP or vehicle placebo.Key findings: Right ventricular hypertrophy and a marked elevation in right ventricular systolic pressure (RVSP) were seen in both models of PH. Rats treated with the combination of SU5416 and chronic hypoxia also developed pulmonary endothelial hyperproliferative lesions. Continuous intravenous infusion of CNP at either dose did not attenuate the development of PH, right ventricular hypertrophy or vascular remodeling in either of the models of PH despite a three-fold increase in serum CNP levels.Significance: CNP does not prevent the development of PH in the chronic hypoxia or SU5416 plus hypoxia models of pulmonary hypertension suggesting that CNP may not play an important modulatory role in human PH. Published by Elsevier Inc.