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首页> 外文期刊>Life sciences >Role of endothelial cells in modulation of contractility induced by hexarelin in rat ventricle.
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Role of endothelial cells in modulation of contractility induced by hexarelin in rat ventricle.

机译：内皮细胞在大鼠心室中由六氢肾上腺素诱导的收缩力调节中的作用。

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摘要

The synthetic growth hormone (GH) secretagogue hexarelin has important cardiac effects, that include a reduction of dysfunction in ischemic-reperfused hearts from GH-deficient rats after a chronic treatment and an increase of ejection fraction in acutely treated men. To investigate the mechanisms of its cardiac activity, we studied the effects of hexarelin (1-10 microM) on contractility of rat papillary muscles. We observed, in hexarelin treated papillary muscles, an improved recovery of contractility after anoxia. Hexarelin induced time- and frequency-dependent inotropic effects on papillary muscle. These effects were a transient increase in contractile force, abolished by propranolol (0.2 microM), followed by a reduction at low (60-240/min), but not at high (400-600/min) beating frequencies. The typical negative force-frequency relationship present in rat papillary muscles was therefore modified, and a minor increase in diastolic tension occurred after a sudden increase in stimulus frequency. Blockade of NO synthesis with 1 mM L-NAME, partially altered the response to hexarelin. MK-677 (1 microM), a non peptidyl GH secretagogue, reduced contractility, but did not alter the force-frequency relationship. The remaining effects of hexarelin were absent in papillary muscles pre-treated with indomethacin (1 microM), or after removal of endocardial endothelium with 0.5% triton X-100. The release of the prostacyclin metabolite 6-keto-PGF1alpha was increased during reoxygenation after a period of anoxia in hexarelin treated papillary muscles. Hexarelin had no significant effect on calcium transients and on I(Ca) measured in isolated ventricular cells. These findings suggest that the effects of hexarelin are mainly due to endothelium-released PGI2.
机译：合成生长激素（GH）促分泌素六氢肾上腺素具有重要的心脏作用，包括长期治疗后减少GH缺陷大鼠缺血再灌注心脏的功能障碍，以及急性治疗男性的射血分数增加。为了研究其心脏活动的机制，我们研究了六氢萘酚（1-10 microM）对大鼠乳头肌收缩力的影响。我们观察到，在用hexarelin处理的乳头肌中，缺氧后收缩力的恢复有所改善。 Hexarelin诱导乳头肌的时间依赖性和频率依赖性正性肌力作用。这些作用是收缩力的短暂增加，被普萘洛尔（0.2 microM）消除，然后在低（60-240 / min）的情况下降低，但在高（400-600 / min）的搏动频率下却没有降低。因此，在大鼠乳头肌中存在的典型的负力-频率关系得到了改善，并且在突然增加刺激频率后，舒张压出现了轻微的增加。用1 mM L-NAME阻断NO合成，部分改变了对hexarelin的反应。 MK-677（1 microM），一种非肽基GH促分泌素，可收缩性降低，但并未改变力-频率关系。在用吲哚美辛（1 microM）预处理的乳头肌中，或在用0.5％Triton X-100去除心内膜内皮后，乳头肌中均未见到hexarelin的其余作用。氧氟沙星处理过的乳头肌缺氧一段时间后，在复氧过程中前列环素代谢物6-酮-PGF1α的释放增加。 Hexarelin对孤立的心室细胞中的钙瞬变和I（Ca）均无显着影响。这些发现表明，hexarelin的作用主要归因于内皮释放的PGI2。

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