Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation

Guido Boerrigter, Lisa C. Costello-Boerrigter, Gail J. Harty, Harald Lapp, John C. Burnett

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Brain natriuretic peptide (BNP 1-32) plays an important physiologic role in cardiorenal homeostasis. Recently, it has been reported that BNP 1-32 is rapidly cleaved by the ubiquitous enzyme dipeptidyl peptidase IV to BNP 3-32, which lacks the two NH2-terminal amino acids of BNP 1-32. The bioactivity of BNP 3-32 in cardiorenal regulation is unknown. We hypothesized that BNP 3-32 has reduced vasodilating and natriuretic bioactivity compared with BNP 1-32 in vivo. Synthetic human BNP 3-32 and BNP 1-32 were administered to eight anesthetized normal canines. After baseline measurements, BNP 1-32 at 30 ng·kg-1·min-1 was administered, followed by a washout, a postinfusion clearance, and a clearance with an equimolar dose of BNP 3-32. In four studies, the sequence of BNP 1-32 and BNP 3-32 infusion was reversed. Peptides were compared by analyzing the changes from the respective preinfusion clearance to the respective infusion clearance. *P < 0.05 between peptides. BNP 3-32, unlike BNP 1-32, did not decrease mean arterial pressure (0 ± 1 vs. -7 ± 2* mmHg, respectively) and did not increase renal blood flow (+12 ± 10 vs. +52 ± 10* ml/min). Effects on heart rate and cardiac output were similar. Urinary sodium excretion increased 128 ± 18 μeq/min with BNP 3-32 and 338 ± 40* μeq/min with BNP 1-32. Urine flow increased 1.1 ± 0.2 ml/min with BNP 3-32 and 2.8 ± 0.4* ml/min with BNP 1-32. Plasma BNP immunoreactivity was lower with BNP 3-32, suggesting accelerated degradation. In this study, BNP 3-32 showed reduced natriuresis and diuresis and a lack of vasodilating actions compared with BNP 1-32.

Original languageEnglish (US)
Pages (from-to)R897-R901
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • BNP 3-32
  • Cardiorenal regulation
  • Enzymatic degradation product
  • Hormone

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

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