Document Detail

Renal and anti-aldosterone actions of vasopressin-2 receptor antagonism and B-type natriuretic peptide in experimental heart failure.
MedLine Citation:
PMID:  20176717     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Hemodynamic and neurohumoral function can affect the efficacy of diuretic therapy in congestive heart failure. Arginine vasopressin increases water reabsorption through the V(2) receptor in the collecting duct, whereas B-type natriuretic peptide (BNP) decreases sodium reabsorption in the collecting duct. We hypothesized that combining BNP to the V(2)-receptor antagonist tolvaptan (TLV) would enhance renal excretory function by augmenting sodium excretion together with aquaresis without adversely affecting renal hemodynamics in experimental congestive heart failure.
METHODS AND RESULTS: Congestive heart failure was induced in 3 groups (n=6 per group) of dogs by tachypacing. A acute experiment was done after 10 days. After baseline measurements, study groups received a 0.1 mg/kg IV bolus of TLV alone (TLV), TLV in combination with BNP (TLV+BNP; 50 ng/[kg . min]), or BNP alone (BNP). Mean arterial pressure increased with TLV, remained unchanged with TLV+BNP, and decreased with BNP (+5+/-1mm Hg versus -1+/-1 mm Hg versus -15+/-1 mm Hg; P<0.05). Renal blood flow and glomerular filtration rate were preserved with all regimens. Urine flow increased in all 3 groups but significantly more so with TLV+BNP (TLV: +0.4+/-0.1 mL/min versus TLV+BNP: +2.4+/-0.5 mL/min versus BNP: +0.8+/-0.3 mL/min; P<0.05). Only TLV+BNP and BNP were natriuretic (P<0.05), whereas only TLV and TLV+BNP increased electrolyte-free water excretion (P<0.05). Compared with TLV alone, TLV+BNP prevented an increase in aldosterone (P<0.05).
CONCLUSIONS: Coadministration of TLV and BNP in experimental HF resulted in a beneficial profile of renal, neurohumoral, and hemodynamic actions, specifically potent diuresis with natriuresis, neutral effect on mean arterial pressure, and lack of aldosterone activation.
Lisa C Costello-Boerrigter; Guido Boerrigter; Alessandro Cataliotti; Gail J Harty; John C Burnett
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-22
Journal Detail:
Title:  Circulation. Heart failure     Volume:  3     ISSN:  1941-3297     ISO Abbreviation:  Circ Heart Fail     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-07-15     Revised Date:  2011-09-26    
Medline Journal Info:
Nlm Unique ID:  101479941     Medline TA:  Circ Heart Fail     Country:  United States    
Other Details:
Languages:  eng     Pagination:  412-9     Citation Subset:  IM    
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA.
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MeSH Terms
Aldosterone / blood
Benzazepines / administration & dosage*
Blood Pressure / drug effects
Disease Models, Animal
Drug Therapy, Combination
Glomerular Filtration Rate / drug effects
Heart Failure / drug therapy,  metabolism*,  physiopathology*
Natriuretic Agents / administration & dosage*
Natriuretic Peptide, Brain / administration & dosage*
Receptors, Vasopressin / administration & dosage*
Renal Circulation / drug effects
Water-Electrolyte Balance / drug effects
Grant Support
Reg. No./Substance:
0/Benzazepines; 0/Natriuretic Agents; 0/Receptors, Vasopressin; 114471-18-0/Natriuretic Peptide, Brain; 150683-30-0/tolvaptan; 52-39-1/Aldosterone

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