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Am J Physiol Renal Physiol 290: F273-F278, 2006. First published September 27, 2005; doi:10.1152/ajprenal.00195.2005
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INNOVATIVE METHODOLOGY

Vasopressin-2-receptor antagonism augments water excretion without changes in renal hemodynamics or sodium and potassium excretion in human heart failure

Lisa C. Costello-Boerrigter,1 William B. Smith,2 Guido Boerrigter,1 John Ouyang,3 Christopher A. Zimmer,3 Cesare Orlandi,3 and John C. Burnett, Jr.1

1Cardiorenal Research Laboratory, Mayo Clinic and Mayo Clinic College of Medicine, Rochester, Minnesota; 2New Orleans Center for Clinical Research, New Orleans, Louisiana; and 3Otsuka Maryland Research Institute, Rockville, Maryland

Submitted 12 May 2005 ; accepted in final form 22 September 2005

Diuretics are frequently required to treat fluid retention in patients with congestive heart failure (CHF). Unfortunately, they can lead to a decline in renal function, electrolyte depletion, and neurohumoral activation. Arginine vasopressin (AVP) promotes renal water reabsorption via the V2 receptor, and its levels are increased in CHF. This study was designed to assess the effects of a single oral dose of tolvaptan, a selective V2-receptor blocker, in the absence of other medications, on renal function in human CHF and to compare this to the effects of a single oral dose of furosemide. We hypothesized that V2-receptor antagonism would yield a diuresis comparable to furosemide but would not adversely affect renal hemodynamics, plasma electrolyte concentration, or neurohumoral activation in stable human CHF. Renal and neurohumoral effects of tolvaptan and furosemide were assessed in an open-label, randomized, placebo-controlled crossover study in 14 patients with NYHA II-III CHF. Patients received placebo or 30 mg of tolvaptan on day 1 and were crossed over to the other medication on day 3. On day 5, all subjects received 80 mg of furosemide. Tolvaptan and furosemide induced similar diuretic responses. Unlike tolvaptan, furosemide increased urinary sodium and potassium excretion and decreased renal blood flow. Tolvaptan, furosemide, and placebo did not differ with respect to mean arterial pressure, glomerular filtration rate, or serum sodium and potassium. We conclude that tolvaptan is an effective aquaretic with no adverse effects on renal hemodynamics or serum electrolytes in patients with mild to moderate heart failure.

congestive heart failure; V2-receptor antagonism; aquaretics


Address for reprint requests and other correspondence: L. C. Costello-Boerrigter, Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and College of Medicine, 200 First St. SW, Rochester, MN 55905 (e-mail: costello.lisa{at}mayo.edu)




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