Kim Suhn Hee, Koh Gou Young, Cho Kyung Woo, Park Woong-Yang, Seo Jeong-Sun
Department of Physiology, Institute for Medical Sciences, Chonbuk National University Medical School, Jeonju 561-180, Republic of Korea.
Exp Biol Med (Maywood). 2003 Feb;228(2):200-6. doi: 10.1177/153537020322800211.
The mechanical overload of the heart is known to induce the expression of atrial natriuretic peptide (ANP) and heat-shock protein 70 (HSP70) in the heart. However, the relationship between these two substances remains unknown. In the present study, we characterized ANP secretion from mouse atria and examined a possible role that HSP70 may play in the regulation of ANP synthesis and secretion by using atria in transgenic mice in which HSP70 was overexpressed. We generated transgenic mice harboring the human HSP70gene under the transcriptional control of human myosin heavy-chain promoter. In these mice, the transgene was overexpressed in the heart. Both atrial ANP messenger RNA and its concentration in the HSP70 transgenic mice were measured; these were not significantly different from those in wild-type mice. In isolated perfused nonbeating atria, basal secretion of ANP was similar in both groups. When atrial volume was increased by changing atrial pressure, extracellular fluid (ECF) translocation and ANP secretion proportionately increased. Changes in atrial volume and ECF translocation and ANP secretion were positively correlated. However, these parameters did not significantly differ between the two groups. Endothelin-1 (ET-1), the strongest paracrine stimulus of ANP secretion, accentuated stretch-activated ANP secretion without significantly changing mechanically stimulated ECF translocation, as compared with that in the wild-type mice. The increased ANP secretion due to ET-1 in the transgenic mice was similar to that in the wild-type mice. The results suggest that both atrial stretching and ET-1 are important stimuli to ANP secretion from mouse atria, and the responsiveness of the ANP system to those stimuli are unlikely coupled to the pathway involving HSP70.
已知心脏的机械性超负荷会诱导心房利钠肽（ANP）和热休克蛋白70（HSP70）在心脏中的表达。然而，这两种物质之间的关系尚不清楚。在本研究中，我们对小鼠心房的ANP分泌进行了表征，并通过使用HSP70过表达的转基因小鼠的心房，研究了HSP70在调节ANP合成和分泌中可能发挥的作用。我们构建了在人肌球蛋白重链启动子转录控制下携带人HSP70基因的转基因小鼠。在这些小鼠中，转基因在心脏中过表达。我们测量了HSP70转基因小鼠心房ANP信使核糖核酸及其浓度；这些与野生型小鼠中的并无显著差异。在分离的灌注静止心房中，两组的ANP基础分泌相似。当通过改变心房压力增加心房容积时，细胞外液（ECF）转运和ANP分泌相应增加。心房容积、ECF转运和ANP分泌的变化呈正相关。然而，两组之间这些参数并无显著差异。内皮素-1（ET-1）是ANP分泌最强的旁分泌刺激物，与野生型小鼠相比，它增强了牵张激活的ANP分泌，而没有显著改变机械刺激的ECF转运。转基因小鼠中由ET-1引起的ANP分泌增加与野生型小鼠相似。结果表明，心房牵张和ET-1都是小鼠心房ANP分泌的重要刺激物，并且ANP系统对这些刺激的反应性不太可能与涉及HSP70的途径相关联。
