Saijonmaa O, Fyhrquist F
Minerva Institute for Medical Research, Helsinki University Central Hospital, Finland.
Cardiovasc Res. 1998 Oct;40(1):206-10. doi: 10.1016/s0008-6363(98)00103-5.
To examine the role of atrial natriuretic peptide (ANP) and cyclic GMP in the regulation of angiotensin converting enzyme (ACE) in cultured human endothelial cells.
Cultured endothelial cells from human umbilical veins (HUVEC) were treated with ANP (0.3-30 nM), 8-Br-cGMP (1-100 microM), Rp-8-Br-PET-cGMPS (1 microM), or the phosphodiesterase inhibitors, zaprinast (10-100 microM), dipyridamole (1-10 microM), or isobutyl methyl xanthine (IBMX, 0.1-0.5 mM). ACE amounts were measured by inhibitor binding assay and cellular cGMP levels by radioimmunoassay.
ANP caused a dose dependent increase in ACE measured in intact endothelial cell culture. The stimulatory effect of ANP was blocked by Rp-8-Br-PET-cGMPS, a protein kinase G inhibitor. The cyclic GMP analog, 8-Br-cGMP and the cyclic GMP specific phosphodiesterase inhibitor, zaprinast, both increased ACE. Increase of ACE was also caused by nonspecific phosphodiesterase inhibitors, dipyridamole and IBMX. Intracellular cGMP levels were shown to increase by ANP, and phosphodiesterase inhibitors.
These data suggest that cGMP is an intracellular mediator regulating ACE and that ANP induced increase of ACE is mediated via a cGMP dependent mechanism.
研究心房利钠肽（ANP）和环磷酸鸟苷（cGMP）在体外培养的人内皮细胞中对血管紧张素转换酶（ACE）的调节作用。
用ANP（0.3 - 30 nM）、8-溴-cGMP（1 - 100 microM）、Rp-8-溴-PET-cGMPS（1 microM）或磷酸二酯酶抑制剂扎普司特（10 - 100 microM）、双嘧达莫（1 - 10 microM）或异丁基甲基黄嘌呤（IBMX，0.1 - 0.5 mM）处理人脐静脉内皮细胞（HUVEC）。通过抑制剂结合试验测定ACE含量，用放射免疫分析法测定细胞内cGMP水平。
在完整的内皮细胞培养物中，ANP可使ACE呈剂量依赖性增加。蛋白激酶G抑制剂Rp-8-溴-PET-cGMPS可阻断ANP的刺激作用。环磷酸鸟苷类似物8-溴-cGMP和环磷酸鸟苷特异性磷酸二酯酶抑制剂扎普司特均可增加ACE。非特异性磷酸二酯酶抑制剂双嘧达莫和IBMX也可导致ACE增加。ANP和磷酸二酯酶抑制剂均可使细胞内cGMP水平升高。
这些数据表明，cGMP是调节ACE的细胞内介质，ANP诱导的ACE增加是通过cGMP依赖性机制介导的。
