Synthetic salusins as cardiac depressors in rat
Synthetic salusins as cardiac depressors in rat
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DOI：
10.1161/01.hyp.0000156496.15668.62
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发表时间：
2005-03-01
期刊：
影响因子：
8.3
通讯作者：
Shichiri, M
中科院分区：
文献类型：
--
作者：
Izumiyama, H;Tanaka, H;Shichiri, M
通过对全长、丰富的人类cDNA文库的生物信息学分析，我们最近发现了Salusins，一种在人体主要组织中普遍表达的多功能相关多肽。Salusin静脉注射给大鼠可引起短暂而严重的低血压，其中Salusin-beta的降压作用尤为显著。然而，这种降压作用的机制仍然不清楚。为了确定Salusins是否对大鼠心脏功能有调节作用，我们研究了Salusin给药前后大鼠工作和非工作心脏灌流前后系统血流动力学和功能的一系列变化。给完整麻醉大鼠静脉注射Salusin-beta后，在低血压和心动过缓的情况下，主动脉血流量出现暂时性、快速、深度的下降，但不影响全身血管阻力。M受体拮抗剂阿托品可完全阻断Salusin-beta诱发的低血压和心动过缓，但心得安不能阻断。在分离的灌流工作大鼠心脏中，Salusin-beta显著减少心输出量、主动脉流量和每搏功。然而，它并不影响工作心脏和非工作心脏的冠脉流量。我们的结果表明，Salusins通过负性变力和变时性作用诱导有效的降压。Salusin-beta通过促进迷走神经流出到心脏来促进其作用，而salusin-beta的负性肌力作用也通过直接的肌力效应来调节。
Using bioinformatic analyses of full- length, enriched human cDNA libraries, we recently identified salusins, multifunctional related peptides ubiquitously expressed in major human tissues. Salusins cause transient and profound hypotension when injected intravenously to rats, the hypotensive effect of salusin- beta being especially striking. However, the mechanisms of this hypotensive action remain elusive. To determine whether salusins modulate cardiac function in rats, we studied serial changes of systemic hemodynamics and functions of isolated perfused working and nonworking hearts before and after salusin administration. Intravenous salusin- beta administration to intact anesthetized rats caused a temporary rapid, profound decrease in aortic blood flow concomitantly with hypotension and bradycardia without affecting systemic vascular resistance. Salusin- beta - induced hypotension and bradycardia were completely blocked by pretreatment with atropine, a muscarinic receptor antagonist, but not by propranolol. In isolated perfused working rat hearts, salusin- beta significantly decreased cardiac output, aortic flow, and stroke work. However, it did not affect coronary flow in isolated working and nonworking hearts. Our results indicate that salusins induce potent hypotension via negative inotropic and chronotropic actions. Salusin- beta promotes its actions by facilitating vagal outflows to the heart, whereas the negative inotropism of salusin- beta is also mediated via a direct myotropic effect.