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 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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
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.
Luchner
A
A
Klinik und Poliklinik für Innere Medizin II, Klinikum der Universität Regensburg, F.J. Strauss Allee 11, 93042, Regensburg, Germany. andreas.luchner@klinik.uni-regensburg.de
Muders
F
F
Dietl
O
O
Friedrich
E
E
Blumberg
F
F
Protter
A A
AA
Riegger
G A
GA
Elsner
D
D
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000235:genetics / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D004195:Disease Models, Animal; D018450:Disease Progression; D015870:Gene Expression; D006333:Heart Failure / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D020097:Natriuretic Peptide, Brain / Q000235:genetics / Q000378:metabolism*; D009929:Organ Size; D012333:RNA, Messenger / Q000235:genetics; D011817:Rabbits; D018487:Ventricular Dysfunction, Left / Q000378:metabolism*
D012333:RNA, Messenger; D020097:Natriuretic Peptide, Brain; D009320:Atrial Natriuretic Factor