Klinger J R, Siddiq F M, Swift R A, Jackson C, Pietras L, Warburton R R, Alia C, Hill N S
Division of Pulmonary and Critical Care Medicine, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island 02903, USA.
Am J Physiol. 1998 Oct;275(4):L645-52. doi: 10.1152/ajplung.1998.275.4.L645.
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.
心房利钠肽和脑利钠肽（分别为ANP和BNP）是强效的肺血管扩张剂，在低氧适应的大鼠中上调，可能预防低氧性肺动脉高压。为了验证C型利钠肽（CNP）也调节肺血管对低氧反应的假说，我们比较了CNP与ANP对从常氧和低氧适应大鼠获取的肺动脉环、胸主动脉环及离体灌注肺的血管扩张作用。我们还测量了常氧和低氧适应大鼠心脏、肺、脑及血浆中的CNP和ANP水平。通过相对逆转录聚合酶链反应对相同器官中的稳态CNP信使核糖核酸水平进行定量。在预收缩的胸主动脉和肺动脉环以及来自常氧和低氧适应大鼠的离体肺中，CNP作为血管扩张剂的效力低于ANP。慢性低氧使血浆CNP升高（15±2对6±1皮克/毫升；P<0.05），并使右心房（35±14对65±17皮克/毫克蛋白；P<0.05）和肺（3±1对14±3皮克/毫克蛋白；P<0.05）中的CNP降低，但对脑或右心室中的CNP无影响。慢性低氧使右心室中的ANP水平升高五倍（49±5对11±2皮克/毫克蛋白；P<0.05），但对肺或脑中的ANP无影响。右心房中的ANP水平有降低趋势（2009±323对2934±397皮克/毫克蛋白；P=无显著性差异）。除了低氧适应大鼠右心房的CNP信使核糖核酸水平较低外，两组大鼠之间未观察到CNP转录水平的差异。我们得出结论，在常氧和低氧适应大鼠中，CNP作为肺血管扩张剂的效力低于ANP，并且低氧会升高循环中的CNP水平而不增加心肺CNP的表达。这些发现表明，在预防大鼠低氧性肺动脉高压方面，CNP可能不如ANP或BNP重要。
