C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia-adapted rats.
C-type natriuretic peptide expression and pulmonary vasodilation in hypoxia-adapted rats.
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DOI：
10.1152/ajplung.1998.275.4.l645
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发表时间：
1998-10
期刊：
影响因子：
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通讯作者：
J. Klinger;F. Siddiq;R. Swift;C. Jackson;L. Pietras;R. Warburton;C. Alia;N. Hill
中科院分区：
文献类型：
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作者：
J. Klinger;F. Siddiq;R. Swift;C. Jackson;L. Pietras;R. Warburton;C. Alia;N. Hill
心房利钠肽和脑利钠肽（分别为ANP和BNP）是有效的肺血管扩张剂，在低氧适应大鼠中上调，并可防止低氧性肺动脉高压。为了验证C型利钠肽（CNP）也调节肺血管对缺氧的反应这一假设，我们比较了CNP与ANP对肺动脉环、胸主动脉环和离体灌注肺的血管舒张作用，这些肺灌注肺来自常氧和缺氧适应大鼠。我们还测量了在常氧和低氧适应大鼠的心，肺，脑和血浆中的CNP和ANP水平。通过相对RT-PCR定量相同器官中的稳态CNP mRNA水平。CNP是一个较低的有效的血管扩张剂比ANP在预收缩的胸主动脉和肺动脉环，并在离体肺从常氧和缺氧适应大鼠。慢性缺氧增加血浆CNP（15 ± 2 vs. 6 ± 1 pg/ml; P < 0.05），降低右心房（35 ± 14 vs. 65 ± 17 pg/mg蛋白; P < 0.05）和肺（3 ± 1 vs. 14 ± 3 pg/mg蛋白; P < 0.05）中的CNP，但对脑或右心室中的CNP无影响。慢性缺氧使右心室ANP水平增加5倍（49 ± 5 pg/mg蛋白对11 ± 2 pg/mg蛋白; P < 0.05），但对肺或脑中的ANP没有影响。右心房中的ANP水平有降低的趋势（2，009 ± 323 vs 2，934 ± 397 pg/mg蛋白; P =不显著）。除了缺氧适应大鼠右心房CNP mRNA水平较低外，两组大鼠之间未观察到CNP转录水平差异。我们得出的结论是，在常氧和缺氧适应大鼠中，CNP的肺血管扩张作用不如ANP，并且缺氧会提高循环中的CNP水平，但不会增加心肺CNP表达。提示CNP对大鼠缺氧性肺动脉高压的保护作用不如ANP或BNP。
Atrial and brain natriuretic peptides (ANP and BNP, respectively) are potent pulmonary vasodilators that are upregulated in hypoxia-adapted rats and may protect against hypoxic pulmonary hypertension. To test the hypothesis that C-type natriuretic peptide (CNP) also modulates pulmonary vascular responses to hypoxia, we compared the vasodilator effect of CNP with that of ANP on pulmonary arterial rings, thoracic aortic rings, and isolated perfused lungs obtained from normoxic and hypoxia-adapted rats. We also measured CNP and ANP levels in heart, lung, brain, and plasma in normoxic and hypoxia-adapted rats. Steady-state CNP mRNA levels were quantified in the same organs by relative RT-PCR. CNP was a less potent vasodilator than ANP in preconstricted thoracic aortic and pulmonary arterial rings and in isolated lungs from normoxic and hypoxia-adapted rats. Chronic hypoxia increased plasma CNP (15 ± 2 vs. 6 ± 1 pg/ml; P < 0.05) and decreased CNP in the right atrium (35 ± 14 vs. 65 ± 17 pg/mg protein; P < 0.05) and in the lung (3 ± 1 vs. 14 ± 3 pg/mg protein; P < 0.05) but had no effect on CNP in brain or right ventricle. Chronic hypoxia increased ANP levels fivefold in the right ventricle (49 ± 5 vs. 11 ± 2 pg/mg protein; P < 0.05) but had no effect on ANP in lung or brain. There was a trend toward decreased ANP levels in the right atrium (2,009 ± 323 vs. 2,934 ± 397 pg/mg protein; P = not significant). No differences in CNP transcript levels were observed between the two groups of rats except that the right atrial CNP mRNA levels were lower in hypoxia-adapted rats. We conclude that CNP is a less potent pulmonary vasodilator than ANP in normoxic and hypoxia-adapted rats and that hypoxia raises circulating CNP levels without increasing cardiopulmonary CNP expression. These findings suggest that CNP may be less important than ANP or BNP in protecting against hypoxic pulmonary hypertension in rats.