Local Renal Delivery of a Natriuretic Peptide: A Renal-Enhancing Strategy for B-Type Natriuretic Peptide in Overt Experimental Heart Failure

Abstract

The purpose of this study was to test the hypothesis that local renal delivery of B-type natriuretic peptide (BNP) will overcome renal resistance to BNP without systemic hypotension. BNP has vasodilating, natriuretic, and renin-inhibiting properties. In overt heart failure (HF), there is development of renal resistance to BNP. We defined the cardiorenal and humoral effects of systemic (n = 6) or local renal (n = 7) administration of canine BNP (0.01 microg/kg/min) in 2 separate groups of dogs with pacing-induced subacute overt HF complicated by renal dysfunction. We used a commercially available small (3.1-F) bifurcated renal catheter (FlowMedica Inc., Fremont, California) for direct bilateral infusion of BNP into both renal arteries. With systemic BNP at this clinically used dose (without the bolus), urine flow increased, but there was only a trend for an increase in urinary sodium excretion and glomerular filtration rate (GFR). In contrast, local renal delivery of BNP resulted in significant diuresis and natriuresis and an increase in GFR. These diuretic and natriuretic responses were greater with local renal BNP compared with systemic BNP, and were associated with increased delivery of BNP to the renal tubules as evident by a greater urinary BNP excretion resulting in a decrease in distal reabsorption of sodium. Importantly, local renal BNP did not result in a significant decrease in mean arterial pressure that was observed with systemic BNP. We conclude that local renal BNP delivery is a novel strategy that may overcome renal assistance to BNP in overt HF by increasing local delivery of BNP to the renal tubules.