Efficacy of prolonged infusion of urodilatin [ANP-(95-126)] in patients with congestive heart failure.
Urodilatin [ANP-95-126] is a new natriuretic peptide of renal origin not subjected to tolerance in experimental congestive heart failure (CHF). To evaluate its therapeutic potentials in CHF, we investigated the efficacy of a prolonged infusion of urodilatin (15 ng/kg/min for 10 hours) in 12 patients with CHF (New York Heart Association functional classes II and III) in a randomized, double-blind, placebo-controlled study. Urodilatin elevated plasma cyclic guanosine monophosphate (cGMP) concentrations and increased urinary cGMP excretion. Systolic blood pressure (121 +/- 9 mm Hg to 111 +/- 7 mm Hg) and central venous pressure (7.4 +/- 3.3 mm Hg to 5.2 +/- 3.4 mm Hg) decreased significantly, and diastolic blood pressure and heart rate remained unchanged. Urine flow (0.7 +/- 0.6 ml/min to 1.5 +/- .6 ml/min) and urinary sodium excretion (48 +/- 16 mumol/min to 180 +/- 97 mumol/min) were significantly increased. Plasma norepinephrine, renin, aldosterone, and vasopressin were unaltered. The substance was well tolerated. Thus prolonged infusion of urodilatin lowers preload and increases diuresis and natriuresis without neurohumoral activation or adverse side effects, demonstrating a profile of effects that may be beneficial in patients with CHF.
Elsner
D
D
Klinik und Poliklinik für Innere Medizin II, University of Regensburg, Germany.
Muders
F
F
Müntze
A
A
Kromer
E P
EP
Forssmann
W G
WG
Riegger
G A
GA
D000368:Aged; D000450:Aldosterone / Q000097:blood; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000008:administration & dosage* / Q000627:therapeutic use; D006152:Cyclic GMP / Q000378:metabolism; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics / Q000008:administration & dosage* / Q000627:therapeutic use; D004311:Double-Blind Method; D005260:Female; D006333:Heart Failure / Q000188:drug therapy*; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000097:blood; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000627:therapeutic use; D012083:Renin / Q000097:blood; D013997:Time Factors
D004232:Diuretics; D010446:Peptide Fragments; D001127:Arginine Vasopressin; D000450:Aldosterone; C056452:Ularitide; D009320:Atrial Natriuretic Factor; D012083:Renin; D006152:Cyclic GMP; D009638:Norepinephrine