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


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.
Cataliotti
Alessandro
A
Cardiorenal Research Laboratory, Department of Physiology and Internal Medicine, Mayo Clinic and Foundation, Rochester, Minn 55905, USA. cataliotti.alessandro@mayo.edu
Boerrigter
Guido
G
Costello-Boerrigter
Lisa C
LC
Schirger
John A
JA
Tsuruda
Toshihiro
T
Heublein
Denise M
DM
Chen
Horng H
HH
Malatino
Lorenzo S
LS
Burnett
John C
JC
D000818:Animals; D002302:Cardiac Output / Q000187:drug effects; D002304:Cardiac Pacing, Artificial; D006152:Cyclic GMP / Q000097:blood / Q000652:urine; D004231:Diuresis / Q000187:drug effects*; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D005665:Furosemide / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D000451:Mineralocorticoid Receptor Antagonists / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009318:Natriuresis / Q000187:drug effects*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000097:blood; D012079:Renal Circulation / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects
D004232:Diuretics; D000451:Mineralocorticoid Receptor Antagonists; D020097:Natriuretic Peptide, Brain; D005665:Furosemide; D006152:Cyclic GMP; D009638:Norepinephrine