VASODILATORY ACTION OF ENDOGENOUS ATRIAL-NATRIURETIC-FACTOR IN A RAT MODEL OF CHRONIC HEART-FAILURE AS DETERMINED BY MONOCLONAL ANF ANTIBODY
VASODILATORY ACTION OF ENDOGENOUS ATRIAL-NATRIURETIC-FACTOR IN A RAT MODEL OF CHRONIC HEART-FAILURE AS DETERMINED BY MONOCLONAL ANF ANTIBODY
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DOI：
10.1161/01.res.66.5.1371
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发表时间：
1990-05-01
影响因子：
20.1
通讯作者：
JUST, H
中科院分区：
文献类型：
--
作者：
DREXLER, H;HIRTH, C;JUST, H
由于缺乏特异性的抑制物，内源性心钠素(ANF)在慢性心力衰竭中的作用一直难以阐明。我们使用了一种新开发的单抗，该抗体已被证明能在体内特异性地阻断外源性和内源性释放的ANF。为了评价心钠素在慢性心力衰竭中的血管扩张作用，我们将这种抗心钠素的抗体或腹水(对照血清)注射到心肌梗死和心力衰竭大鼠以及假手术动物中。无论是假手术组还是梗死组，腹水都没有改变中心血流动力学。抗体显著增加了梗死组的右房压、左室舒张末压和全身血管阻力(SVR)，但对假手术组的这些变量没有影响。由于放射性微球测量的肾血流量在所有四组中都显著减少，可能是由于腹水的非特异性肾血管收缩作用，所以另一组梗塞动物被纯化的ANF抗体(没有非特异性影响)或小鼠免疫球蛋白作为对照注射。在这些动物中，右房压力从1.1。+-升高。0.7至2.6。+-。0.70毫米汞柱(p<；0.001)。尽管给予纯化的心钠素抗体后，梗塞动物的SVR、肾血流速度(用多普勒探头测量)和肾血管阻力没有改变，但基础血浆ANF值与纯化的ANF抗体引起的SVR的变化之间存在显著的相关性(r=0.758，p<；0.02，n=9)，即高基线血浆ANF(350pg/ml)的大鼠SVR增加，而血浆ANF的动物则减少。
Elucidation of the role of (elevated) endogenous atrial natriuretic factor (ANF) in chronic heart failure has been hampered by a lack of specific inhibitors. We used a newly developed monoclonal antibody that has been shown to specifically block both exogenously and endogenously released ANF in vivo. For assessment of the vasodilatory action of ANF in chronic heart failure, either this antibody against ANF or ascites (control serum) was injected in rats with myocardial infarction and failure and in sham animals. Ascites did not alter central hemodynamics in either the sham or infarcted group. Antibody significantly increased right atrial pressure, left ventricular end-diastolic pressure, and systemic vascular resistance (SVR) in the infarction group but did not affect these variables in the sham group. Because renal blood flow, as measured by radioactive microspheres, decreased significantly in all four groups, probably due to nonspecific renal vasoconstrictor effects of the ascites, a separate group of infarcted animals was treated with purified ANF antibody (devoid of nonspecific effects) or mouse IgG as a control injection. In these animals, right atrial pressure increased from 1.1 .+-. 0.7 to 2.6 .+-. 0.7 mm Hg (p < 0.001). Although SVR, renal blood flow velocity (measured by Doppler probe), and renal vascular resistance did not change in the infarcted animals after administration of purified ANF antibody, a significant correlation was found between baseline plasma ANF values and the change in SVR exerted by purified ANF antibody (r = 0.758, p < 0.02, n = 9); that is, SVR increased in rats with high baseline plasma ANF (>350 pg/ml), but decreased in animals with plasma ANF