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

Horng Haur Chen, Alessandro Cataliotti, John A. Schirger, Fernando L. Martin, Lynn K. Harstad, John C Jr. Burnett

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Objectives: 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. Background: BNP has vasodilating, natriuretic, and renin-inhibiting properties. In overt heart failure (HF), there is development of renal resistance to BNP. Methods: We defined the cardiorenal and humoral effects of systemic (n = 6) or local renal (n = 7) administration of canine BNP (0.01 μg/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. Results: 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. Conclusions: 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.

Original languageEnglish (US)
Pages (from-to)1302-1308
Number of pages7
JournalJournal of the American College of Cardiology
Volume53
Issue number15
DOIs
StatePublished - Apr 14 2009

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Natriuretic Peptides
Brain Natriuretic Peptide
Heart Failure
Kidney
Glomerular Filtration Rate
Sodium
Natriuresis
Diuresis
Renal Artery

Keywords

  • heart failure
  • natriuretic peptides
  • renal function

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Local Renal Delivery of a Natriuretic Peptide. A Renal-Enhancing Strategy for B-Type Natriuretic Peptide in Overt Experimental Heart Failure. / Chen, Horng Haur; Cataliotti, Alessandro; Schirger, John A.; Martin, Fernando L.; Harstad, Lynn K.; Burnett, John C Jr.

In: Journal of the American College of Cardiology, Vol. 53, No. 15, 14.04.2009, p. 1302-1308.

Research output: Contribution to journalArticle

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abstract = "Objectives: 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. Background: BNP has vasodilating, natriuretic, and renin-inhibiting properties. In overt heart failure (HF), there is development of renal resistance to BNP. Methods: We defined the cardiorenal and humoral effects of systemic (n = 6) or local renal (n = 7) administration of canine BNP (0.01 μg/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. Results: 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. Conclusions: 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.",
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AU - Cataliotti, Alessandro

AU - Schirger, John A.

AU - Martin, Fernando L.

AU - Harstad, Lynn K.

AU - Burnett, John C Jr.

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