Modulation of the renin-angiotensin pathway through enzyme inhibition and specific receptor blockade in pacing-induced heart failure: II. Effects on myocyte contractile processes.
Modulation of the renin-angiotensin pathway through enzyme inhibition and specific receptor blockade in pacing-induced heart failure: II. Effects on myocyte contractile processes.
复制标题
在起搏引起的心力衰竭中通过酶抑制和特异性受体阻断来调节肾素-血管紧张素通路：II。
DOI：
10.1161/01.cir.96.7.2397
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发表时间：
1997
期刊：
影响因子：
37.8
通讯作者：
deGasparo,M
中科院分区：
文献类型：
--
作者：
Spinale,FG;Mukherjee,R;Iannini,JP;Whitebread,S;Hebbar,L;Clair,MJ;Melton,DM;Cox,MH;Thomas,PB;deGasparo,M
背景本研究的目的是确定在充血性心力衰竭（CHF）模型中单独的ACE抑制（ACEI）、单独的AT 1血管紧张素（Ang）II受体阻断剂以及联合的ACEI和AT 1 Ang II受体阻断剂对LV功能、全身血流动力学和神经激素系统活性的影响。（1）快速心房起搏（240 bpm）3周（n=9），（2）ACEI（3）AT 1Ang Ⅱ受体阻断剂（4）ACEI和AT 1Ang Ⅱ受体阻断剂（5）假手术对照组（n=10）。起搏组左室短轴缩短率（LVFS）下降（13.4±1.4% vs 39.1±1.0%），舒张末期内径（LVEDD）增加（5.61±0.11 vs 3.45±0.07 cm）（P<0.05）。在AT 1Ang II阻断和快速起搏的情况下，LVEDD和LVFS与仅起搏值相比没有变化。ACEI使LVEDD（4.95±0.11 cm）降低，LVFS（20.9±1.9%）增加（P<0.05）。ACEI和AT 1Ang Ⅱ阻断使LVEDD降低（4.68±0.07 cm），LVFS增加（25.2±0.9%）（P<0.05）。血浆去甲肾上腺素和内皮素增加超过5倍，慢性起搏和保持升高与AT 1Ang II阻滞。ACEI组和联合用药组的血浆去甲肾上腺素水平比单纯起搏组降低了两倍以上。ACEI和AT 1血管紧张素II受体阻滞剂降低血浆内皮素水平从rapid-pacing values.ConclusionsThese研究结果表明，ACEI在CHF的设置中的影响不仅是由于调节血管紧张素II水平，而是替代酶的途径，并结合ACEI和AT 1血管紧张素II受体阻滞剂可能提供独特的好处，左心室泵功能和神经激素系统的设置CHF。
BackgroundThe goal of this study was to determine the effects of ACE inhibition (ACEI) alone, AT1angiotensin (Ang) II receptor blockade alone, and combined ACEI and AT1Ang II receptor blockade on LV function, systemic hemodynamics, and neurohormonal system activity in a model of congestive heart failure (CHF).Methods and ResultsPigs were randomly assigned to each of 5 groups: (1) rapid atrial pacing (240 bpm) for 3 weeks (n=9), (2) ACEI (benazeprilat, 0.187 mg · kg−1· d−1) and rapid pacing (n=9), (3) AT1Ang II receptor blockade (valsartan, 3 mg · kg−1· d−1) and rapid pacing (n=9), (4) ACEI and AT1Ang II receptor blockade (benazeprilat/valsartan, 0.05/3 mg · kg−1· d−1) and rapid pacing (n=9), and (5) sham controls (n=10). In the pacing group, LV fractional shortening (LVFS) fell (13.4±1.4% versus 39.1±1.0%) and end-diastolic dimension (LVEDD) increased (5.61±0.11 versus 3.45±0.07 cm) compared with control (P<.05). With AT1Ang II blockade and rapid pacing, LVEDD and LVFS were unchanged from pacing-only values. ACEI reduced LVEDD (4.95±0.11 cm) and increased LVFS (20.9±1.9%) from pacing-only values (P<.05). ACEI and AT1Ang II blockade reduced LVEDD (4.68±0.07 cm) and increased LVFS (25.2±0.9%) from pacing only (P<.05). Plasma norepinephrine and endothelin increased by more than fivefold with chronic pacing and remained elevated with AT1Ang II blockade. Plasma norepinephrine was reduced from pacing-only values by more than twofold in the ACEI group and the combination group. ACEI and AT1Ang II receptor blockade reduced plasma endothelin levels by >50% from rapid-pacing values.ConclusionsThese findings suggest that the effects of ACEI in the setting of CHF are not solely due to modulation of Ang II levels but rather to alternative enzymatic pathways and that combined ACEI and AT1Ang II receptor blockade may provide unique benefits for LV pump function and neurohormonal systems in the setting of CHF.