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

2007 ◽  
Vol 2007 ◽  
pp. 339-342
Author(s):  
M.D. Cheitlin
Keyword(s):  
Heart Failure ◽  
Human Heart ◽  
Renal Hemodynamics ◽  
Potassium Excretion ◽  
Human Heart Failure ◽  
Water Excretion ◽  
Receptor Antagonism ◽  
Sodium And Potassium

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

2006 ◽  
Vol 290 (2) ◽  
pp. F273-F278 ◽  
Author(s):  
Lisa C. Costello-Boerrigter ◽  
William B. Smith ◽  
Guido Boerrigter ◽  
John Ouyang ◽  
Christopher A. Zimmer ◽  
...  
Keyword(s):  
Heart Failure ◽  
Renal Function ◽  
Oral Dose ◽  
Single Oral Dose ◽  
Renal Hemodynamics ◽  
Potassium Excretion ◽  
Water Excretion ◽  
Receptor Antagonism ◽  
Neurohumoral Activation ◽  
Sodium And Potassium

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.

Increased Cardiac Adrenergic Drive Precedes Generalized Sympathetic Activation in Human Heart Failure

Circulation ◽  
1997 ◽  
Vol 95 (1) ◽  
pp. 169-175 ◽  
Author(s):  
Bengt Rundqvist ◽  
Mikael Elam ◽  
Yrsa Bergmann-Sverrisdottir ◽  
Graeme Eisenhofer ◽  
Peter Friberg
Keyword(s):  
Heart Failure ◽  
Human Heart ◽  
Sympathetic Activation ◽  
Human Heart Failure

scholarly journals The Ku Protein Complex Interacts with YY1, Is Up-Regulated in Human Heart Failure, and Represses α Myosin Heavy-Chain Gene Expression

2004 ◽  
Vol 24 (19) ◽  
pp. 8705-8715 ◽  
Author(s):  
Carmen C. Sucharov ◽  
Steve M. Helmke ◽  
Stephen J. Langer ◽  
M. Benjamin Perryman ◽  
Michael Bristow ◽  
...  
Keyword(s):  
Heart Failure ◽  
Myosin Heavy Chain ◽  
Heavy Chain ◽  
Human Heart ◽  
Ventricular Myocytes ◽  
Major Effect ◽  
Neonatal Rat ◽  
Chain Gene ◽  
Human Heart Failure ◽  
Peptide Mass

ABSTRACT Human heart failure is accompanied by repression of genes such as α myosin heavy chain (αMyHC) and SERCA2A and the induction of fetal genes such as βMyHC and atrial natriuretic factor. It seems likely that changes in MyHC isoforms contribute to the poor contractility seen in heart failure, because small changes in isoform composition can have a major effect on the contractility of cardiac myocytes and the heart. Our laboratory has recently shown that YY1 protein levels are increased in human heart failure and that YY1 represses the activity of the human αMyHC promoter. We have now identified a region of the αMyHC promoter that binds a factor whose expression is increased sixfold in failing human hearts. Through peptide mass spectrometry, we identified this binding activity to be a heterodimer of Ku70 and Ku80. Expression of Ku represses the human αMyHC promoter in neonatal rat ventricular myocytes. Moreover, overexpression of Ku70/80 decreases αMyHC mRNA expression and increases skeletal α-actin. Interestingly, YY1 interacts with Ku70 and Ku80 in HeLa cells. Together, YY1, Ku70, and Ku80 repress the αMyHC promoter to an extent that is greater than that with YY1 or Ku70/80 alone. Our results suggest that Ku is an important factor in the repression of the human αMyHC promoter during heart failure.

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