Lohmeier T E, Mizelle H L, Reinhart G A, Montani J P, Hord C E, Didlake R H
Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson 39216-4505, USA.
Am J Physiol. 1996 Nov;271(5 Pt 2):R1353-63. doi: 10.1152/ajpregu.1996.271.5.R1353.
The purpose of this study was to determine whether high plasma levels of atrial natriuretic peptide (ANP) in compensated heart failure are important in the maintenance of sodium balance. This was achieved by subjecting eight dogs to bilateral atrial appendectomy (APX) to blunt the ANP response to pacing-induced heart failure. Five intact dogs served as controls. In controls, 14 days of left ventricular pacing at 240 beats/min produced a sustained fall in cardiac output and mean arterial pressure of approximately 40 and 20%, respectively; compared with cardiac output, reductions in renal blood flow (up to approximately 25%) were less pronounced and even smaller decrements in GFR occurred (up to 9%). Despite these changes and a threefold elevation in plasma norepinephrine concentration, plasma renin activity (PRA) did not increase and sodium balance was achieved during the second week of pacing in association with a six- to eightfold rise in plasma levels of ANP. Similar responses occurred in four dogs in which APX was relatively ineffective in blunting the ANP response to pacing. In marked contrast, there were substantial increments in PRA and in plasma norepinephrine concentration, and marked sodium and water retention during the last week of pacing in four dogs with APX and severely deficient ANP. These results indicate that ANP plays a critical role in promoting sodium excretion in the early stages of cardiac dysfunction.
本研究的目的是确定在代偿性心力衰竭中,高血浆水平的心房利钠肽(ANP)在维持钠平衡方面是否重要。这是通过对八只狗进行双侧心耳切除术(APX)以减弱ANP对起搏诱导的心力衰竭的反应来实现的。五只完整的狗作为对照。在对照组中,以240次/分钟的频率进行14天的左心室起搏,使心输出量和平均动脉压分别持续下降约40%和20%;与心输出量相比,肾血流量的减少(高达约25%)不太明显,肾小球滤过率的下降幅度更小(高达9%)。尽管有这些变化以及血浆去甲肾上腺素浓度升高了三倍,但血浆肾素活性(PRA)并未增加,并且在起搏的第二周实现了钠平衡,同时血浆ANP水平升高了六至八倍。在四只APX对减弱ANP对起搏的反应相对无效的狗中也出现了类似的反应。与之形成鲜明对比的是,在四只APX且ANP严重缺乏的狗中,在起搏的最后一周,PRA和血浆去甲肾上腺素浓度大幅增加,并且出现了明显的钠和水潴留。这些结果表明,ANP在心脏功能障碍的早期阶段促进钠排泄方面起着关键作用。