Renal actions of synthetic dendroaspis natriuretic peptide.
BACKGROUND
Dendroaspis natriuretic peptide (DNP), recently isolated from the venom of the green Mamba snake Dendroaspis angusticeps, is a 38 amino acid peptide containing a 17 amino acid disulfide ring structure similar to that of atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP). DNP-like immunoreactivity (DNP-LI) was reported to be present in human plasma and atrial myocardium and to be elevated in human congestive heart failure. Although previously named DNP, it remains unknown if DNP is natriuretic or if is it present in canine plasma, urine, and atrial myocardium.


METHODS
Studies were performed in vivo in anesthetized dogs (N = 6) using intravenous infusion of synthetic DNP at 10 and 50 ng/kg/min. Employing a sensitive and specific radioimmunoassay for DNP, the presence of DNP-like peptide was assessed in the canine plasma and urine before, during, and following the administration of exogenous synthetic DNP. Additionally, we performed immunohistochemical studies using the indirect immunoperoxidase method with polyclonal DNP antiserum in normal atrial myocardium (N = 10). Atrial concentrations of DNP-LI were also assessed.


RESULTS
We report that DNP is markedly natriuretic and diuretic, which, like ANP and BNP, is associated with the increase in urinary and plasma cGMP. DNP-like peptide is also detected in canine plasma, urine, and atrial myocardium.


CONCLUSIONS
These studies establish that DNP is a potent natriuretic and diuretic peptide with tubular actions linked to cGMP and that DNP may play a physiological role in the regulation of sodium excretion.
Lisy
O
O
Cardiorenal Research Laboratory, Division of Cardiovascular Diseases, Department of Physiology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA. lisy.ondrej2@mayo.edu
Jougasaki
M
M
Heublein
D M
DM
Schirger
J A
JA
Chen
H H
HH
Wennberg
P W
PW
Burnett
J C
JC
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure; D006152:Cyclic GMP / Q000378:metabolism; D004285:Dogs; D004546:Elapid Venoms / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D006325:Heart Atria / Q000737:chemistry; D006333:Heart Failure / Q000097:blood; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D009206:Myocardium / Q000737:chemistry; D010455:Peptides / Q000032:analysis / Q000737:chemistry / Q000493:pharmacokinetics*; D012964:Sodium / Q000652:urine; D014556:Urine
C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D012964:Sodium; D006152:Cyclic GMP