Loke K E, Messina E J, Mital S, Hintze T H
Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
J Mol Cell Cardiol. 2000 Dec;32(12):2299-306. doi: 10.1006/jmcc.2000.1258.
We investigated the role of kinin and nitric oxide (NO) in the modulation of cardiac O(2)consumption in Syrian hamsters with overt heart failure (HF) and age-matched normal hamsters. Using echocardiography, the hamsters with heart failure had reduced ejection fraction [31(+/-8) v 76(+/-5)%] and LV dilation [4.9(+/-0. 2) v 5.7(+/-0.3) mm, both P<0.05 from normal]. O(2)consumption in the left ventricular free wall was measured using a Clark-type O(2)electrode in an air-tight chamber, containing Krebs solution buffered with Hepes (37 degrees C, pH 7.4). Concentration response curves to bradykinin (BK), ramiprilat (RAM), amlodipine (AMLO) and the NO donor, S -nitroso- N -acetyl-penicillamine (SNAP) were performed. Basal myocardial O(2)consumption was lower in the HF group compared to normal [316(+/-21) v 404(+/-36) nmol O(2)/min/g, respectively, P<0.05]. In the hearts from normal hamsters BK (10(-4)mol/l), RAM (10(-4)mol/l), and AMLO (10(-5)mol/l) all significantly reduced myocardial O(2)consumption by 42(+/-6)%, 29(+/-7)% and 27(+/-5)% respectively. This reduction was attenuated in the presence of N -nitro- l -arginine methyl ester (l -NAME) [BK: 3.3(+/-1.5)%, RAM: 3.3(+/-1.2)%, AMLO: 2.3(+/-1.2)%, P<0.05]. Interestingly in the hearts from HF group, BK, RAM and AMLO caused a significantly smaller reduction in myocardial O(2)consumption [10(+/-2)%, 2.5(+/-1.3)%, 6.3(+/-2.3)%, P<0.05]. In contrast, the NO donor SNAP reduced myocardial O(2)consumption in both groups and all those responses were not affected by l -NAME. These data indicate that endogenous NO production through the kinin-dependent mechanism is impaired at end-stage heart failure. The loss of kinin and NO control of mitochondrial respiration may contribute to the pathogenesis of heart failure.
我们研究了激肽和一氧化氮（NO）在明显心力衰竭（HF）的叙利亚仓鼠及年龄匹配的正常仓鼠心脏氧消耗调节中的作用。通过超声心动图检查，心力衰竭仓鼠的射血分数降低[31（±8）对76（±5）%]，左心室扩张[4.9（±0.2）对5.7（±0.3）mm，两者与正常相比P<0.05]。使用Clark型氧电极在含有用Hepes缓冲的Krebs溶液（37℃，pH 7.4）的气密室中测量左心室游离壁的氧消耗。进行了对缓激肽（BK）、雷米普利拉（RAM）、氨氯地平（AMLO）和NO供体S-亚硝基-N-乙酰青霉胺（SNAP）的浓度反应曲线。HF组的基础心肌氧消耗低于正常组[分别为316（±21）对404（±36）nmol O₂/分钟/克，P<0.05]。在正常仓鼠的心脏中，BK（10⁻⁴mol/l）、RAM（10⁻⁴mol/l）和AMLO（10⁻⁵mol/l）分别使心肌氧消耗显著降低42（±6）%、29（±7）%和27（±5）%。在存在N-硝基-L-精氨酸甲酯（L-NAME）的情况下，这种降低减弱[BK：3.3（±1.5）%，RAM：3.3（±1.2）%，AMLO：2.3（±1.2）%，P<0.05]。有趣的是，在HF组的心脏中，BK、RAM和AMLO引起的心肌氧消耗降低明显较小[10（±2）%，2.5（±1.3）%，6.3（±2.3）%，P<0.05]。相反，NO供体SNAP在两组中均降低了心肌氧消耗，且所有这些反应均不受L-NAME影响。这些数据表明，在终末期心力衰竭时，通过激肽依赖性机制产生的内源性NO受损。激肽和NO对线粒体呼吸控制的丧失可能导致心力衰竭的发病机制。
