Sustained Cardiovascular Actions of APJ Agonism During Renin-Angiotensin System Activation and in Patients With Heart Failure
Sustained Cardiovascular Actions of APJ Agonism During Renin-Angiotensin System Activation and in Patients With Heart Failure
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DOI：
10.1161/circheartfailure.111.000077
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发表时间：
2013-05-01
影响因子：
9.7
通讯作者：
Newby, David E.
中科院分区：
文献类型：
--
作者：
Barnes, Gareth D.;Alam, Shirjel;Newby, David E.
背景-为了评估APJ激动剂在长时间（Pyr（1））apelin-13输注和reninangiotensin system activation.Methods和Results-48名志愿者和12名慢性稳定性心力衰竭患者参加了一系列随机安慰剂对照研究。分别采用双侧静脉闭塞体积描记法、生物阻抗心动图、经胸超声心动图和血压计测量前臂血流量、心脏指数、左心室尺寸和平均动脉压，在简短的当地（0.3-3.0 nmol/min）和全身（30-300 nmol/min）或全身延长（30 nmol/min）（Pyr（1））在存在或不存在血管紧张素-血管紧张素系统激活的情况下输注爱帕琳-13，伴钠耗尽或血管紧张素II联合输注。在钠耗竭和血管紧张素II联合输注期间，（Pyr（1））apelin-13诱导的血管舒张得以保留（两者P< 0.02）。全身静脉（Pyr（1））apelin-13输注增加心脏指数，而降低平均动脉压和外周血管阻力指数（P< 0.001），无论钠耗竭或血管紧张素II（0.5 ng/kg/min）共输注（P>0.05）。延长6小时（Pyr（1））apelin-13输注导致慢性心力衰竭患者心脏指数持续增加，左心室射血分数增加（ANOVA; P< 0.001）。APJ激动剂可能是补充慢性心力衰竭患者当前最佳药物治疗的主要希望。
Background-To assess cardiovascular actions of APJ agonism during prolonged (Pyr(1)) apelin-13 infusion and reninangiotensin system activation.Methods and Results-Forty-eight volunteers and 12 patients with chronic stable heart failure attended a series of randomized placebo-controlled studies. Forearm blood flow, cardiac index, left ventricular dimensions, and mean arterial pressure were measured using bilateral venous occlusion plethysmography, bioimpedance cardiography, transthoracic echocardiography, and sphygmomanometry, respectively, during brief local (0.3-3.0 nmol/min) and systemic (30-300 nmol/min) or prolonged systemic (30 nmol/min) (Pyr(1)) apelin-13 infusions in the presence or absence of renin-angiotensin system activation with sodium depletion or angiotensin II coinfusion. During sodium depletion and angiotensin II coinfusion, (Pyr(1)) apelin-13-induced vasodilatation was preserved (P< 0.02 for both). Systemic intravenous (Pyr(1)) apelin-13 infusion increased cardiac index, whereas reducing mean arterial pressure and peripheral vascular resistance index (P< 0.001 for all) irrespective of sodium depletion or angiotensin II (0.5 ng/kg per minute) coinfusion (P>0.05 for all). Prolonged 6-hour (Pyr(1)) apelin-13 infusion caused a sustained increase in cardiac index with increased left ventricular ejection fraction in patients with chronic heart failure (ANOVA; P< 0.001 for all).Conclusions-APJ agonism has sustained cardiovascular effects that are preserved in the presence of renin-angiotensin system activation or heart failure. APJ agonism may hold major promise to complement current optimal medical therapy in patients with chronic heart failure.