Xu T, Jiao J H, Pence R A, Baertschi A J
Department of Molecular Physiology, University of Virginia Health Sciences Center, Charlottesville 22908, USA.
Am J Physiol. 1996 Dec;271(6 Pt 2):H2339-45. doi: 10.1152/ajpheart.1996.271.6.H2339.
Perfused hearts (n = 127) were exposed to acute hypoxia (10% O2 for 12 or 20 min) or left atrial stretch (increase in atrial pressure) in the presence or absence of 100 mumol/l ATP-sensitive potassium channel blocker (tolbutamide) or openers (pinacidil and diazoxide). Hypoxia alone elicited a prolonged atrial natriuretic factor (ANF) release, peaking at 74% over baseline (P < 0.01); with tolbutamide, ANF secretion peaked at 132% over baseline (P < 0.01). Pinacidil and diazoxide abolished the ANF response to hypoxia (P < 0.01). Atrial stretch alone (1 mmHg) transiently (2 min) increased ANF by 56% (P < 0.05); with tolbutamide, ANF increased transiently by 124% and showed a prolonged increase of 52% (P < 0.05). With tolbutamide, graded stretch (0.5-2.3 mmHg) induced a bell-shaped transient (2-min) increase of ANF release [-3% at 0.5 mmHg, 124% (P < 0.05) at 1.0 mmHg, 80% (P < 0.05) at 1.48 mmHg, and 14% at 2.22 mmHg] and a saturating prolonged ANF response. Tolbutamide increased the ANF response nonsignificantly at lower doses (30 mumol/l) and had no effect at 1 mumol/l. Pinacidil abolished the stretch-induced ANF release. These results suggest that ATP-sensitive potassium channels are extremely potent modulators of stimulated ANF secretion.
将127颗灌注心脏在存在或不存在100 μmol/L ATP敏感性钾通道阻滞剂（甲苯磺丁脲）或开放剂（匹那地尔和二氮嗪）的情况下暴露于急性缺氧（10%氧气，持续12或20分钟）或左心房牵张（心房压力增加）。单独缺氧引起心房利钠因子（ANF）释放延长，峰值比基线高74%（P<0.01）；使用甲苯磺丁脲时，ANF分泌峰值比基线高132%（P<0.01）。匹那地尔和二氮嗪消除了ANF对缺氧的反应（P<0.01）。单独的心房牵张（1 mmHg）使ANF短暂（2分钟）增加56%（P<0.05）；使用甲苯磺丁脲时，ANF短暂增加124%，并显示出52%的持续增加（P<0.05）。使用甲苯磺丁脲时，分级牵张（0.5 - 2.3 mmHg）诱导ANF释放呈钟形短暂（2分钟）增加[-0.5 mmHg时为-3%，1.0 mmHg时为124%（P<0.05），1.48 mmHg时为80%（P<0.05），2.22 mmHg时为14%]以及饱和的ANF持续反应。甲苯磺丁脲在较低剂量（30 μmol/L）时对ANF反应的增加无显著意义，在1 μmol/L时无作用。匹那地尔消除了牵张诱导的ANF释放。这些结果表明，ATP敏感性钾通道是刺激的ANF分泌的极强调节剂。
