Luchner A, Muders F, Dietl O, Friedrich E, Blumberg F, Protter A A, Riegger G A, Elsner D
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, F.J. Strauss Allee 11, 93042, Regensburg, Germany.
Cardiovasc Res. 2001 Aug 15;51(3):601-7. doi: 10.1016/s0008-6363(01)00316-9.
Activation of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) is considered a hallmark of myocardial remodeling. To determine magnitude and relative proportion of activation during the progression to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rapid ventricular pacing-induced heart failure in rabbits.
Six animals underwent progressive pacing with incremental rates (330 beats per min (bpm) to 380 bpm over 30 days), resulting in congestive heart failure (CHF). Five animals underwent pacing at 330 bpm for 10 days only (early LV dysfunction, ELVD) and five additional animals served as control group (CTRL).
ELVD was characterized by decreased mean arterial pressure (P=0.05 vs. CTRL) as well as significantly impaired LV function (LV fractional shortening (FS) P<0.01 vs. CTRL) and dilatation (P<0.01 vs. CTRL). CHF was characterized by further decreased mean arterial pressure (P<0.01 vs. ELVD), further impaired LV function (FS P<0.03 vs. ELVD) and dilatation (P<0.01 vs. CTRL). In control animals, significant ANP expression was observed only in atrial tissue (P<0.02 vs. BNP) while BNP expression was ubiquitous but marginal (LV P<0.05 vs. ANP). In ELVD, activation of ANP (atria and LV P<0.05 vs. CTRL) and BNP (atria P<0.05 vs. CTRL, LV n.s.) was observed. In CHF, LV-BNP increased further markedly (P<0.01 vs. CTRL, P<0.05 vs. ELVD) while atrial ANP and BNP expression as well as LV ANP expression remained unchanged (all P=n.s. vs. ELVD).
The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditions and during the progression to heart failure and provide a molecular basis for the superiority of BNP as marker of LV dysfunction and CHF.
心房利钠肽（ANP）和脑利钠肽（BNP）的激活被认为是心肌重塑的一个标志。为了确定在进展为心力衰竭过程中激活的程度和相对比例，我们在新建立的家兔快速心室起搏诱导的进行性心力衰竭模型中，评估了心房和左心室（LV）组织中ANP和BNP的基因表达。
6只动物以递增速率（30天内从每分钟330次心跳（bpm）增加到380 bpm）进行逐步起搏，导致充血性心力衰竭（CHF）。5只动物仅以330 bpm起搏10天（早期左心室功能障碍，ELVD），另外5只动物作为对照组（CTRL）。
ELVD的特征是平均动脉压降低（与CTRL相比，P = 0.05）以及左心室功能显著受损（左心室缩短分数（FS）与CTRL相比，P < 0.01）和扩张（与CTRL相比，P < 0.01）。CHF的特征是平均动脉压进一步降低（与ELVD相比，P < 0.01），左心室功能进一步受损（FS与ELVD相比，P < 0.03）和扩张（与CTRL相比，P < 0.01）。在对照动物中，仅在心房组织中观察到显著的ANP表达（与BNP相比，P < 0.02），而BNP表达普遍但较低（左心室与ANP相比，P < 0.05）。在ELVD中，观察到ANP（心房和左心室与CTRL相比，P < 0.05）和BNP（心房与CTRL相比，P < 0.05，左心室无显著性差异）的激活。在CHF中，左心室BNP进一步显著增加（与CTRL相比，P < 0.01，与ELVD相比，P < 0.05），而心房ANP和BNP表达以及左心室ANP表达保持不变（与ELVD相比，所有P = 无显著性差异）。
目前的研究表明，在正常情况下以及进展为心力衰竭的过程中，心房和左心室ANP和BNP的激活存在差异，并为BNP作为左心室功能障碍和CHF标志物的优越性提供了分子基础。
