Evans H G, Lewis M J, Shah A M
University of Wales College of Medicine, Health Park, Cardiff, United Kingdom.
Cardiovasc Res. 1994 Nov;28(11):1694-9. doi: 10.1093/cvr/28.11.1694.
The aim was to study the potential role of basal endothelin-1 release from endocardial endothelium in isolated ferret papillary muscle preparations.
The following interventions were studied: (1) no treatment (time control); (2) endothelin-1 (5 nM); (3) endothelin-1 (5 nM) in the presence of the specific ETA receptor antagonist, BQ123 (10 microM); (4) BQ123 (10 microM) in endocardium-intact muscles; and (5) BQ123 (10 microM) in endocardium-denuded muscles (n = 6 in each group).
Untreated muscles remained stable throughout the experiment. BQ123 fully inhibited the positive inotropic effect of exogenous endothelin-1. In endocardium-intact preparations (n = 6), exposure to BQ123 induced a progressively earlier onset and time course of isometric twitch relaxation [time to peak tension -12.3(SEM 1.8)%, relaxation half time -13.3(1.1)%; both p < 0.01], but had no effect on peak tension or on rate of tension development. Selective denudation of endocardial endothelium induced similar relaxant effects, but also significantly reduced peak tension. In endocardial endothelium-denuded preparations (n = 6), addition of BQ123 did not result in further contractile changes.
Endocardial endothelium in situ on papillary muscle preparations tonically releases endothelin, resulting in a significantly delayed onset of isometric twitch relaxation. There is no evidence for basal endothelin-1 release from microvascular endothelial cells in this superfused preparation. A similar release of endothelin-1 from endocardial endothelium in the intact heart could influence myocardial contractile behaviour independently of changes in coronary perfusion. Endothelin-1 may have a physiological role in modulating myocardial relaxation.
本研究旨在探讨在分离的雪貂乳头肌标本中，心内膜内皮细胞基础释放内皮素-1的潜在作用。
研究了以下干预措施：(1) 不治疗（时间对照）；(2) 内皮素-1（5 nM）；(3) 在特异性ETA受体拮抗剂BQ123（10 μM）存在的情况下加入内皮素-1（5 nM）；(4) 在完整心内膜的肌肉中加入BQ123（10 μM）；(5) 在去除心内膜的肌肉中加入BQ123（10 μM）（每组n = 6）。
未经处理的肌肉在整个实验过程中保持稳定。BQ123完全抑制了外源性内皮素-1的正性肌力作用。在完整心内膜的标本中（n = 6），加入BQ123可使等长收缩舒张的起始时间和时程逐渐提前[达到峰值张力的时间 -12.3（标准误1.8）%，舒张半衰期 -13.3（1.1）%；均p < 0.01]，但对峰值张力或张力发展速率无影响。选择性去除心内膜内皮可诱导类似的舒张作用，但也显著降低了峰值张力。在去除心内膜内皮的标本中（n = 6），加入BQ123未导致进一步的收缩变化。
乳头肌标本上的心内膜内皮可持续释放内皮素，导致等长收缩舒张的起始时间显著延迟。在这种灌流标本中，没有证据表明微血管内皮细胞会基础释放内皮素-1。完整心脏中心内膜内皮类似地释放内皮素-1可能独立于冠状动脉灌注变化而影响心肌收缩行为。内皮素-1可能在调节心肌舒张方面具有生理作用。
