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Am J Physiol Regul Integr Comp Physiol. 2007 Feb;292(2):R897-901. Epub 2006 Oct 26.

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

Author information

1
Cardiorenal Research Laboratory, Guggenheim 915, Mayo Clinic and Mayo Clinic College of Medicine, 200 First St. SW, Rochester, MN 55905, USA. boerrigter.guido@mayo.edu

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 x kg(-1) x 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 microeq/min with BNP 3-32 and 338 +/- 40* microeq/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.

PMID:
17068158
DOI:
10.1152/ajpregu.00569.2006
[Indexed for MEDLINE]
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