Brain natriuretic peptide enhances renal actions of furosemide and suppresses furosemide-induced aldosterone activation in experimental heart failure

Alessandro Cataliotti, Guido Boerrigter, Lisa C Costello-Boerrigter, John A Schirger, Toshihiro Tsuruda, Denise M Heublein, Horng H Chen, Lorenzo S Malatino, John C Burnett
Circulation 2004 April 6, 109 (13): 1680-5

BACKGROUND: The renal actions of brain natriuretic peptide (BNP) in congestive heart failure (CHF) are associated with increased diuresis and natriuresis, preserved glomerular filtration rate (GFR), and lack of activation of the renin-angiotensin-aldosterone system (RAAS). In contrast, diuretic-induced natriuresis may be associated with reduced GFR and RAAS activation. The objective of this study was to test the hypothesis that exogenous BNP enhances the renal diuretic and natriuretic actions of furosemide (Fs) and retards the activation of aldosterone in a model of CHF.

METHODS AND RESULTS: CHF was produced in 2 groups of dogs by ventricular pacing. One group received continuous (90-minute) intravenous Fs (1 mg x kg(-1) x h(-1)). A second group (Fs+BNP) received 45-minute intravenous coinfusion of Fs (1 mg x kg(-1) x h(-1)) and low-dose (2 pmol x kg(-1) x min(-1)) BNP followed by 45-minute coinfusion of Fs (1 mg x kg(-1) x h(-1)) and high-dose (10 pmol x kg(-1) x min(-1)) BNP. Fs increased urinary flow, but the effect of Fs+BNP was greater. Similarly, urinary sodium excretion was higher in the Fs+BNP group. Although GFR tended to decrease in the Fs group, it increased in the Fs+BNP group (35+/-3 to 56+/-4*) (* indicates P<0.05 versus baseline) (P<0.0001 between groups). Plasma aldosterone increased with Fs (41+/-10 to 100+/-11* ng/dL) but was attenuated in the Fs+BNP group (44+/-11 to 54+/-9 ng/dL low-dose and to 47+/-7 ng/dL high-dose) (P=0.0007 between groups).

CONCLUSIONS: Fs+BNP has more profound diuretic and natriuretic responses than Fs alone and also increases GFR without activation of aldosterone. Coadministration of BNP and loop diuretic is effective in maximizing natriuresis and diuresis while preserving renal function and inhibiting activation of aldosterone.

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