Differential expression of cardiac ANP and BNP in a rabbit model of progressive left ventricular dysfunction

Objective: Activation of atrial natriuretic peptide (ANP) and brain natriur etic peptide (BNP) is considered a hallmark of myocardial remodeling. To de termine magnitude and relative proportion of activation during the progress ion to heart failure, we assessed ANP and BNP gene expression in atrial and left ventricular (LV) tissue in a newly developed model of progressive rap id ventricular pacing-induced heart failure in rabbits. Methods: Six animal s underwent progressive pacing with incremental rates (330 beats per min (b pm) 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 dysfunc tion, ELVD) and five additional animals served as control group (CTRL). Res ults: ELVD was characterized by decreased mean arterial pressure (P=0.05 vs . CTRL) as well as significantly impaired LV function (LV fractional shorte ning (FS) P <0.01 vs. CTRL) and dilatation (P <0.01 vs. CTRL). CHF was char acterized by further decreased mean arterial pressure (P <0.01 vs. ELVD), f urther impaired LV function (FS P <0.03 vs. ELVD) and dilatation (P <0.01 v s. 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 C HF, 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 u nchanged (all P=n.s. vs. ELVD). Conclusion: The current studies demonstrate differential activation of atrial and LV ANP and BNP under normal conditio ns and during the progression to heart failure and provide a molecular basi s for the superiority of BNP as marker of LV dysfunction and CHF. (C) 2001 Elsevier Science BY All rights reserved.