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


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.
Costello-Boerrigter
Lisa C
LC
Cardiorenal Research Laboratory, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. costello.lisa@mayo.edu
Boerrigter
Guido
G
Cataliotti
Alessandro
A
Harty
Gail J
GJ
Burnett
John C
JC
D000450:Aldosterone / Q000097:blood; D000818:Animals; D001552:Benzazepines / Q000008:administration & dosage*; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004285:Dogs; D004359:Drug Therapy, Combination; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006333:Heart Failure / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology*; D008297:Male; D045283:Natriuretic Agents / Q000008:administration & dosage*; D020097:Natriuretic Peptide, Brain / Q000008:administration & dosage*; D017483:Receptors, Vasopressin / Q000008:administration & dosage*; D012079:Renal Circulation / Q000187:drug effects; D000077602:Tolvaptan; D014882:Water-Electrolyte Balance / Q000187:drug effects
D001552:Benzazepines; D045283:Natriuretic Agents; D017483:Receptors, Vasopressin; D020097:Natriuretic Peptide, Brain; D000077602:Tolvaptan; D000450:Aldosterone