在轻度和重度实验性心力衰竭中,对急性中性内酶抑制的反应
H H Chen1, J A Schirger, W L Chau
1Cardiorenal Research Laboratory, Division of Cardiovascular Diseases and Department of Physiology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. chen.horng@mayo.edu
Circulation
|December 14, 1999
概括
中性内皮酶 (NEP) 抑制在轻度充血性心力衰竭 (CHF) 中增强功能. 这种方法增加了分泌和脏血流,为早期心脏不全症提供了潜在的治疗策略.
科学领域:
- 心血管生理学心血管生理学
- 药理学 药理学是指药理学的学科.
背景情况:
- 中性内酶24.11 (NEP) 降解了像ANP这样的尿性.
- 轻度充血性心力衰竭 (CHF) 显示ANP增加而没有氨酸- ангиотензин-阿尔多斯特系统 (RAAS) 激活.
- 严重的CHF涉及保留和同活性ANP和RAAS.
研究的目的:
- 调查NEP抑制剂康多克萨特里拉特在患有不同阶段的慢性心血管衰竭的狗中对急性心脏和脏的影响.
- 为了比较NEP抑制在轻度CHF与严重CHF的疗效,并评估AT(1) 受体对抗的影响.
主要方法:
- 研究了四组麻醉狗:正常的,轻度的CHF,严重的CHF和严重的CHF与慢性AT1受体对抗性.
- 轻度和严重的CHF是由快速心室节奏诱导的.
- 通过测量尿路分泌,淋巴膜过率,脏血液流动和ANP/cGMP分泌来评估康多克萨特利的急性心作用.
主要成果:
- 与对照和严重的CHF相比,NEP抑制在轻度的CHF中显著增加了尿路分泌和膜过率.
- 脏血液流量增加,而脏血管抵抗和远端管状的再吸收仅在轻度心血管衰竭下降.
- 尿液中的ANP和cGMP分泌在轻度的CHF中最高;这些影响在严重的CHF中减弱,而不是通过AT(1) 受体对抗改善.
结论:
- 急性NEP抑制显著增强脏血液动力学和分泌在轻度的CHF.
- 这些发现突显了NEP抑制的治疗潜力,以改善选择性ANP激活在早期CHF的功能.
- 在严重的慢性心力衰竭中,NEP抑制对脏的有益作用会减弱,并且通过阻断RAAS通过AT(1) 受体而无法恢复.
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