Natriuretic peptide receptors and neutral endopeptidase in mediating the renal actions of a new therapeutic synthetic natriuretic peptide dendroaspis natriuretic peptide

J Am Coll Cardiol. 2002 Sep 18;40(6):1186-91. doi: 10.1016/s0735-1097(02)02127-7.


Objectives: The objectives of the current study were to define for the first time the roles of the natriuretic peptide (NP) receptors and neutral endopeptidase (NEP) in mediating and modulating the renal actions of Dendroaspis natriuretic peptide (DNP), a new therapeutic synthetic NP.

Background: Recent reports have advanced the therapeutic potential of a newly described synthetic NP called DNP. Dendroaspis natriuretic peptide is a 38-amino acid peptide recently isolated from the venom of Dendroaspis augusticeps (the green mamba snake).

Methods: Synthetic DNP was administered intra-renally at 5 ng/kg/min to 11 normal anesthetized dogs, 5 of which received the NP receptor antagonist HS-142-1 (3 mg/kg intravenous bolus) while the remaining 6 dogs received an infusion of the NEP inhibitor, candoxatrilat (8 and 80 microg/kg/min) (Pfizer, Sandwich United Kingdom).

Results: Intra-renal DNP resulted in marked natriuresis associated with increased urinary cyclic guanosine monophosphate excretion (UcGMPV), glomerular filtration rate (GFR), and renal blood flow (RBF) and decreased distal fractional sodium reabsorption (FNaR) compared with baseline. HS-142-1 attenuated the natriuretic response to DNP, resulting in decreased UcGMPV, GFR, and RBF and increased distal FNaR. In contrast, low and high doses of NEP inhibitor did not potentiate the renal actions of DNP.

Conclusions: We report that the NP receptor blockade attenuated the renal actions of synthetic DNP and that the NEP inhibitor did not alter the renal response to DNP. This latter finding is a unique property of synthetic DNP, as distinguished from other known NPs, supporting its potential as a therapeutic agent.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Dogs
  • Elapid Venoms / pharmacology*
  • Hemodynamics / drug effects
  • Hemodynamics / physiology
  • Intercellular Signaling Peptides and Proteins
  • Kidney / drug effects*
  • Kidney / physiopathology*
  • Male
  • Neprilysin / drug effects*
  • Neprilysin / physiology*
  • Peptides / pharmacology*
  • Receptors, Atrial Natriuretic Factor / drug effects*
  • Receptors, Atrial Natriuretic Factor / physiology*
  • Renal Circulation / drug effects
  • Renal Circulation / physiology


  • Dendroaspis natriuretic peptide
  • Elapid Venoms
  • Intercellular Signaling Peptides and Proteins
  • Peptides
  • Neprilysin
  • Receptors, Atrial Natriuretic Factor