Lü Shun-yan, Zhu Miao-zhang, Wang Dian-shi, Yu Jun, Guo Hai-tao, Hu Yu-zhen, Wei Qi-ming
Department of Physiology, Fourth Military Medical University, Xi-an 710032, China.
Acta Pharmacol Sin. 2004 Apr;25(4):424-30.
To investigate the regulatory effects of vasonatrin peptide (VNP) on the expression of C-type natriuretic peptide receptor (NPR-C) in cultured neonatal rat cardiac myocytes and fibroblasts.
Quantitative RT-PCR was undertaken to evaluate the levels of NPR-C mRNA and radioimmunoassay was used to determine the formation of intracellular cGMP.
Twenty-four hours hypoxic exposure increased the level of NPR-C mRNA in cardiomyocytes, while did not alter the expression of NPR-C in cardiac fibroblasts. VNP (10(-8)-10(-6) mol/L) reduced the levels of NPR-C mRNA in cardiac myocytes induced by hypoxia in a concentration-dependent manner, and with high concentration (10(-6) mol/L) also decreased the expression of NPR-C in cardiac fibroblasts and air-control cardiac myocytes. The inhibitory effects of VNP on the expression of NPR-C was mimicked by 8-bromo-cGMP 10(-6) mol/L (a membrane permeable analog of cGMP). VNP (10(-8)-10(-6) mol/L) increased the formation of intracellular guanosine-3',5'-cyclic monophosphate (cGMP) in both cardiac myocytes and fibroblasts. HS-142-1, the particulate guanylyl cyclase-coupled receptor antagonist, partially abrogated the above effects of VNP.
Hypoxic exposure for 24 h up-regulated the expression of NPR-C in cultured neonatal rat cardiac myocytes. VNP decreased the expression of NPR-C in cardiac myocytes and fibroblasts under both air-control and hypoxic condition, which was at least partially mediated by guanylate cyclase linked natriuretic peptide receptors through increasing the intracellular cGMP.
研究血管钠肽（VNP）对培养的新生大鼠心肌细胞和成纤维细胞中C型利钠肽受体（NPR-C）表达的调节作用。
采用定量逆转录聚合酶链反应（RT-PCR）评估NPR-C mRNA水平，并用放射免疫分析法测定细胞内cGMP的生成。
24小时低氧暴露增加了心肌细胞中NPR-C mRNA的水平，但未改变心脏成纤维细胞中NPR-C的表达。VNP（10^(-8)-10^(-6)mol/L）以浓度依赖的方式降低了低氧诱导的心肌细胞中NPR-C mRNA的水平，高浓度（10^(-6)mol/L）时也降低了心脏成纤维细胞和常氧对照心肌细胞中NPR-C的表达。10^(-6)mol/L的8-溴-cGMP（一种可透过细胞膜的cGMP类似物）模拟了VNP对NPR-C表达的抑制作用。VNP（10^(-8)-10^(-6)mol/L）增加了心肌细胞和成纤维细胞中细胞内鸟苷-3',5'-环磷酸（cGMP）的生成。颗粒型鸟苷酸环化酶偶联受体拮抗剂HS-142-1部分消除了VNP的上述作用。
24小时低氧暴露上调了培养的新生大鼠心肌细胞中NPR-C的表达。VNP在常氧和低氧条件下均降低了心肌细胞和成纤维细胞中NPR-C的表达，这至少部分是通过鸟苷酸环化酶连接的利钠肽受体增加细胞内cGMP介导的。
