Des-serine-proline brain natriuretic peptide 3-32 in cardiorenal regulation.
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.
Boerrigter
Guido
G
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
Costello-Boerrigter
Lisa C
LC
Harty
Gail J
GJ
Lapp
Harald
H
Burnett
John C
JC
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D018819:Dipeptidyl Peptidase 4 / Q000737:chemistry; D004231:Diuresis / Q000187:drug effects; D004285:Dogs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006728:Hormones / Q000097:blood; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D007677:Kidney Function Tests; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000138:chemical synthesis / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000502:physiology; D012079:Renal Circulation / Q000187:drug effects; D014563:Urodynamics / Q000502:physiology; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects; D014882:Water-Electrolyte Balance / Q000187:drug effects / Q000502:physiology
D006728:Hormones; D018377:Neurotransmitter Agents; D020097:Natriuretic Peptide, Brain; D018819:Dipeptidyl Peptidase 4