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.