Renal and anti-aldosterone actions of vasopressin-2 receptor antagonism and B-type natriuretic peptide in experimental heart failure

Lisa C. Costello-Boerrigter, Guido Boerrigter, Alessandro Cataliotti, Gail J. Harty, John C. Burnett

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

Background: Hemodynamic and neurohumoral function can affect the efficacy of diuretic therapy in congestive heart failure. Arginine vasopressin increases water reabsorption through the V2 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 V2- 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.

Original languageEnglish (US)
Pages (from-to)412-419
Number of pages8
JournalCirculation: Heart Failure
Volume3
Issue number3
DOIs
StatePublished - May 2010

Keywords

  • Arginine vasopressin
  • Experimental model
  • Heart failure
  • Kidney
  • Natriuretic peptides
  • Pharmacology
  • V receptor antagonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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