Tavi P, Laine M, Voutilainen S, Lehenkari P, Vuolteenaho O, Ruskoaho H, Weckström M
Departments of Physiology, Division of Biophysics and Biocenter Oulu, University of Oulu, FIN-90220 Oulu, Finland.
Am J Physiol. 1999 Jul;277(1):H405-12. doi: 10.1152/ajpheart.1999.277.1.H405.
We sought to investigate whether atrial myocyte contraction and secretion of the atrial natriuretic peptide (ANP) are affected in the same manner by intervention in intracellular Ca(2+) handling by acidosis. The effects of propionate (20 mM)-induced intracellular acidosis on the stretch-induced changes in ANP secretion, contraction force, and intracellular Ca(2+) concentration (Ca(2+)) were studied in the isolated rat atrium. The stretch of the atrium was produced by increasing the intra-atrial pressure of the paced and superfused preparation. Contraction force was estimated from pressure pulses generated by the contraction of the atrium. Intracellular Ca(2+) was measured from indo 1-AM-loaded atria, and ANP was measured by radioimmunoassay from the perfusate samples collected during interventions. Intracellular pH of the atrial myocytes was measured by a fluorescent indicator (BCECF)-based imaging system. Intracellular acidification caused by 20 mM propionic acid (0.18 pH units) potentiated the stretch-induced (intra-atrial pressure from 1 to 4 mmHg) ANP secretion, causing a twofold secretion compared with nonacidotic controls. Simultaneously, the responsiveness of the atrial contraction to stretch was reduced (P < 0.05, n = 7). Stretch augmented the systolic indo 1-AM transients in acidic (P < 0.05, n = 6) and nonacidic atria (P < 0.05, n = 6). However, during acidosis this was accompanied by an increase of the diastolic indo 1-AM ratio (P < 0.05, n = 6). Cooccurrence of stretch and acidosis caused an increase in systolic and diastolic Ca(2+) and potentiated the stretch-induced ANP secretion, whereas the contraction force and its stretch sensitivity were decreased. This mechanism may be involved in ischemia-induced ANP secretion, suggesting a role for ANP secretion as an indicator of contractile dysfunction.
我们试图研究酸中毒对细胞内Ca(2+)处理的干预是否以相同方式影响心房肌细胞收缩和心房利钠肽（ANP）分泌。在离体大鼠心房中研究了丙酸盐（20 mM）诱导的细胞内酸中毒对拉伸诱导的ANP分泌、收缩力和细胞内Ca(2+)浓度（[Ca(2+)]i）变化的影响。心房的拉伸通过增加起搏和灌注标本的心房内压产生。收缩力通过心房收缩产生的压力脉冲估算。从负载indo 1-AM的心房测量细胞内Ca(2+)，并通过放射免疫分析法从干预期间收集的灌注液样本中测量ANP。通过基于荧光指示剂（BCECF）的成像系统测量心房肌细胞的细胞内pH。20 mM丙酸引起的细胞内酸化（0.18个pH单位）增强了拉伸诱导的（心房内压从1至4 mmHg）ANP分泌，与非酸中毒对照相比，分泌增加了两倍。同时，心房收缩对拉伸的反应性降低（P < 0.05，n = 7）。拉伸增强了酸性（P < 0.05，n = 6）和非酸性心房（P < 0.05，n = 6）中indo 1-AM的收缩期瞬变。然而，在酸中毒期间，这伴随着舒张期indo 1-AM比率的增加（P < 0.05，n = 6）。拉伸和酸中毒同时出现导致收缩期和舒张期[Ca(2+)]i增加，并增强了拉伸诱导的ANP分泌，而收缩力及其拉伸敏感性降低。该机制可能参与缺血诱导的ANP分泌，提示ANP分泌作为收缩功能障碍指标的作用。
