Lakshminrusimha S, D'Angelis C A, Russell J A, Nielsen L C, Gugino S F, Nickerson P A, Steinhorn R H
Department of Pediatrics, State University of New York at Buffalo, Buffalo, New York 14214, USA.
Am J Physiol Lung Cell Mol Physiol. 2001 Aug;281(2):L361-8. doi: 10.1152/ajplung.2001.281.2.L361.
C-type natriuretic peptide (CNP) is a recently described endothelium-derived relaxing factor. CNP relaxes vascular smooth muscle and inhibits smooth muscle proliferation by binding to natriuretic peptide receptor (NPR) type B (NPR-B) and producing cGMP. Lung parenchyma and fifth-generation pulmonary arteries (PA) and veins (PV) were isolated from late-gestation fetal lambs. All three types of NPR mRNA were detected in PA and PV by RT-PCR. CNP and NPR-B immunostaining was positive in pulmonary vascular endothelium and medial smooth muscle. CNP concentration-response curves of PA and PV were compared with those of atrial natriuretic peptide (ANP) by use of standard tissue bath techniques. CNP relaxed PV significantly better than PA. ANP relaxed PA and PV equally, but ANP relaxed PA significantly better than CNP. Pretreating PA and PV with natriuretic peptide receptor blocker (HS-142-1) or cGMP-dependent protein kinase inhibitor Rp-beta-phenyl-1- N2-etheno-8-bromoguanosine 3',5'-cyclic monophosphorothionate significantly inhibited the CNP relaxation response, indicating that the response was mediated through the NPR-cGMP pathway. We conclude that CNP is important in mediating pulmonary venous tone in the fetus.
C型利钠肽（CNP）是最近发现的一种内皮源性舒张因子。CNP通过与B型利钠肽受体（NPR-B）结合并产生环磷酸鸟苷（cGMP）来舒张血管平滑肌并抑制平滑肌增殖。从妊娠晚期胎羊中分离出肺实质、第五代肺动脉（PA）和肺静脉（PV）。通过逆转录聚合酶链反应（RT-PCR）在PA和PV中检测到所有三种类型的NPR mRNA。肺血管内皮和中层平滑肌中CNP和NPR-B免疫染色呈阳性。使用标准组织浴技术比较了PA和PV的CNP浓度-反应曲线与心房利钠肽（ANP）的浓度-反应曲线。CNP对PV的舒张作用明显优于PA。ANP对PA和PV的舒张作用相同，但ANP对PA的舒张作用明显优于CNP。用利钠肽受体阻滞剂（HS-142-1）或cGMP依赖性蛋白激酶抑制剂Rp-β-苯基-1-N2-乙烯基-8-溴鸟苷3',5'-环一磷酸硫代酯预处理PA和PV可显著抑制CNP的舒张反应，表明该反应是通过NPR-cGMP途径介导的。我们得出结论，CNP在调节胎儿肺静脉张力中起重要作用。
