Effects of BG9719 (CVT-124), an A1-adenosine receptor antagonist, and furosemide on glomerular filtration rate and natriuresis in patients with congestive heart failure.
OBJECTIVE
To determine the effects of furosemide and the selective A1 adenosine receptor BG9719 on renal function in patients with congestive heart failure (CHF).


BACKGROUND
Studies suggest that adenosine may affect renal function by various mechanisms, but the effects of blockade of this system in humans is unknown. In addition, the effects of a therapeutic dose of furosemide on glomerular filtration rate (GFR) and renal plasma flow (RPF) in heart failure patients are controversial.


METHODS
On different days, 12 patients received placebo, BG9719 and furosemide. Glomerular filtration rate, RPF and sodium and water excretion were assessed immediately following drug administration.


RESULTS
Glomerular filtration rate was 84 +/- 23 ml/min/1.73m2 after receiving placebo, 82 +/- 24 following BG9719 administration and a decreased (p < 0.005) 63 +/- 18 following furosemide. Renal plasma flow was unchanged at 293 +/- 124 ml/min/1.73m2 on placebo, 334 +/- 155 after receiving BG9719 and 374 +/- 231 after receiving furosemide. Sodium excretion increased from 8 +/- 8 mEq following placebo administration to 37 +/- 26 mEq following BG9719 administration. In the six patients in whom it was measured, sodium excretion was 104 +/- 78 mEq following furosemide administration.


CONCLUSIONS
Natriuresis is effectively induced by both furosemide and the adenosine A1 antagonist BG9719 in patients with CHF. Doses of the two drugs used in this study did not cause equivalent sodium and water excretion but only furosemide decreased GFR. These data suggest that adenosine is an important determinant of renal function in patients with heart failure.
Gottlieb
S S
SS
Department of Medicine, University of Maryland School of Medicine, Baltimore 21201, USA. sgottlie@medicine.umaryland.edu
Skettino
S L
SL
Wolff
A
A
Beckman
E
E
Fisher
M L
ML
Freudenberger
R
R
Gladwell
T
T
Marshall
J
J
Cines
M
M
Bennett
D
D
Liittschwager
E B
EB
D000328:Adult; D000368:Aged; D004232:Diuretics / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000008:administration & dosage* / Q000009:adverse effects; D005919:Glomerular Filtration Rate / Q000187:drug effects* / Q000502:physiology; D006333:Heart Failure / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D007677:Kidney Function Tests; D008297:Male; D008875:Middle Aged; D009318:Natriuresis / Q000187:drug effects* / Q000502:physiology; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1 / Q000502:physiology; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology; D014970:Xanthines / Q000008:administration & dosage* / Q000009:adverse effects
C097280:1,3-dipropyl-8-(2-(5,6-epoxy)norbornyl)xanthine; D004232:Diuretics; D058915:Purinergic P1 Receptor Antagonists; D018047:Receptors, Purinergic P1; D014970:Xanthines; D005665:Furosemide