Cardiorenal and endocrine effects of synthetic canine BNP1-32 in dogs with compensated congestive heart failure caused by myxomatous mitral valve disease

Abstract

Background: The effects of synthetic brain natriuretic peptide (BNP1-32) on cardiorenal and renin angiotensin aldosterone system in dogs with naturally occurring congestive heart failure (CHF) are unknown.

Objectives: To evaluate the cardiorenal and endocrine effects of SC administered synthetic canine BNP1-32, with or without furosemide, in dogs with CHF caused by myxomatous mitral valve disease (MMVD).

Animals: Seven client-owned male dogs with compensated American College of Veterinary Internal Medicine stage C CHF caused by MMVD on chronic treatment with furosemide, benazepril, and pimobendan.

Methods: A single-dose, crossover, pilot study. Each dog received a dose of BNP1-32 (5 μg/kg), furosemide (2 mg/kg), and both BNP1-32/furosemide (5 μg/kg and 2 mg/kg, respectively) SC with a 2-week washout period among each treatment. Between- and within-treatment effects were evaluated using linear mixed modeling with restricted maximum likelihood estimation and evaluation of least square differences.

Results: Rapid absorption of BNP1-32 and a corresponding rise in urinary cyclic guanosine monophosphate excretion was observed at 1-2 hours after any treatment containing BNP1-32 (P < .05). However, BNP1-32 did not influence measured cardiorenal variables. Plasma aldosterone concentrations were below quantifiable levels in majority of the samples.

Conclusions and clinical importance: No beneficial cardiorenal effects were detected. It is possible that dogs with chronic CHF have a reduction in natriuretic peptide responsiveness.

Keywords: RAAS; aldosterone; brain natriuretic peptide; cGMP; canine.

Figure 1

Plasma concentrations of immunoreactive BNP‐32 (pg/mL; graph A) and cGMP (pM/mL; graph B) after administration of BNP1‐32 (5 μg/kg, solid black line), furosemide (2 mg/kg, solid gray line), or BNP1‐32 + furosemide (5 μg/kg + 2 mg/kg, dashed black line) SC in 7 dogs with chronic congestive heart failure caused by myxomatous mitral valve disease. The median and range were plotted. Asterisks denote significant (P < .05) differences between BNP1‐32 and furosemide (*) and BNP1‐32 + furosemide and furosemide (***). Hats denote significant (P < .05) differences from baseline for BNP1‐32 (^∧) and BNP1‐32 + furosemide (^{∧ ∧ ∧})

Figure 2

Urinary excretion of cGMP (pM/kg/min; graph A) and fractional excretions of sodium (FE_Na, %; graph B) and potassium (FE_K, %; graph C) after administration of BNP1‐32 (5 μg/kg, solid black line), furosemide (2 mg/kg, solid gray line), or BNP1‐32 + furosemide (5 μg/kg + 2 mg/kg, dashed black line) SC in 7 dogs with chronic congestive heart failure caused by myxomatous mitral valve disease. The median and range were plotted. Asterisks denote significant (P < .05) differences between BNP1‐32 and furosemide (*); BNP1‐32 and BNP1‐32 + furosemide (**); and BNP1‐32 + furosemide and furosemide (***). Hats denote significant (P < .05) differences from baseline for BNP1‐32 (^∧); furosemide (^{∧ ∧}); and BNP1‐32 + furosemide (^{∧ ∧ ∧})

Figure 3

Plasma concentrations of aldosterone (nM/L) after administration of BNP1‐32 (5 μg/kg, solid black line), furosemide (2 mg/kg, solid gray line), or BNP1‐32 + furosemide (5 μg/kg + 2 mg/kg, dashed black line) SC in 7 dogs with chronic congestive heart failure caused by myxomatous mitral valve disease. The lowest limit of quantification (LLOQ) of the assay was 0.070 nM/L. All concentrations < LLOQ were estimated to be half the LLOQ

Figure 4

Urine output (UOP) after administration of BNP1‐32 (5 μg/kg, solid black line), furosemide (2 mg/kg, solid gray line), or BNP1‐32 + furosemide (5 μg/kg + 2 mg/kg, dashed black line) SC in 7 dogs with chronic congestive heart failure caused by myxomatous mitral valve disease. The median and range were plotted. Asterisks denote significant (P < .05) differences between BNP1‐32 and furosemide (*); and BNP1‐32 and BNP1‐32 + furosemide (**). Hats denote significant (P < .05) differences from baseline for furosemide (^{∧ ∧}) and BNP1‐32 + furosemide (^{∧ ∧ ∧})

Figure 5

Systolic blood pressure (SBP; graph A), diastolic blood pressure (DBP; graph B), mean blood pressure (MBP; graph C), and heart rate (HR; graph D) after administration of BNP1‐32 (5 μg/kg, solid black line), furosemide (2 mg/kg, solid gray line), or BNP1‐32 + furosemide (5 μg/kg + 2 mg/kg, dashed black line) SC in 7 dogs with chronic congestive heart failure caused by myxomatous mitral valve disease. The median and range were plotted