Yoshida H, Nakamura M, Makita S, Hiramori K
Second Department of Internal Medicine, Iwate Medical University, Morioka, Japan.
J Atheroscler Thromb. 1994;1(2):76-9. doi: 10.5551/jat1994.1.76.
This study investigated the effect of atrial natriuretic peptide (ANP) on endothelin (ET) secretion from cultured human endothelial cells. Confluent umbilical venous endothelial cells were incubated with experimental agents in multi-well plates, and the level of immunoreactive ET in the medium was measured by radioimmunoassay. There was no significant effect of ANP (10(-8), 10(-7) and 10(-6) M) on ET secretion after a 3- or 6-hour incubation. However, with 24-hour incubation, ANP significantly inhibited ET secretion from cultured human endothelial cells (control, 139.0 +/- 7.2 fmol/well; 10(-7) M, 89.4 +/- 4.7 fmol/well; 10(-7) M, 79.4 +/- 8.2 fmol/well; 10(-6) M, 71.0 +/- 10.1 fmol/well, P < 0.01). Furthermore, the addition of 8-bromo-cyclic GMP to the medium inhibited ET secretion (control, 147.2 +/- 2.9 fmol/well; 10(-5) M, 140.9 +/- 2.3 fmol/well; 10(-4) M, 143.0 +/- 1.0 fmol/well; 10(-3) M, 96.6 +/- 6.3 fmol/well, P < 0.01). These findings demonstrate that ANP inhibits accelerated ET secretion from cultured human endothelial cells, probably due to augmentation of intracellular cyclic GMP levels by ANP-activated guanylate cyclase.
本研究调查了心房利钠肽(ANP)对培养的人内皮细胞分泌内皮素(ET)的影响。将汇合的脐静脉内皮细胞在多孔板中与实验试剂一起孵育,通过放射免疫测定法测量培养基中免疫反应性ET的水平。孵育3小时或6小时后,ANP(10^(-8)、10^(-7)和10^(-6) M)对ET分泌无显著影响。然而,孵育24小时后,ANP显著抑制培养的人内皮细胞分泌ET(对照组,139.0±7.2 fmol/孔;10^(-7) M,89.4±4.7 fmol/孔;10^(-7) M,79.4±8.2 fmol/孔;10^(-6) M,71.0±10.1 fmol/孔,P<0.01)。此外,向培养基中添加8-溴环鸟苷酸可抑制ET分泌(对照组,147.2±2.9 fmol/孔;10^(-5) M,140.9±2.3 fmol/孔;10^(-4) M,143.0±1.0 fmol/孔;10^(-3) M,96.6±6.3 fmol/孔,P<0.01)。这些发现表明,ANP抑制培养的人内皮细胞加速分泌ET,这可能是由于ANP激活的鸟苷酸环化酶增加了细胞内环鸟苷酸水平。