Dendroaspis natriuretic peptide relaxes isolated human arteries and veins.
BACKGROUND
Dendroaspis natriuretic peptide (DNP) is the newest member of the natriuretic peptide family and is a circulating peptide in humans. The effects of DNP on the human vasculature are unknown. Since other natriuretic peptides are known to cause vasorelaxation, we determined the response to DNP on human blood vessels in vitro. We also investigated the mechanism of DNP mediated vasorelaxation.


METHODS
Rings of human internal mammary artery and saphenous vein were suspended in an organ bath. The response to cumulative concentrations of DNP was obtained. Inhibiting agents were used to determine the mechanism of this vasorelaxation.


RESULTS
DNP caused dose-dependent relaxation, with a greater effect on the internal mammary arteries (relaxation from 10(-7) mol/l DNP: 80.6+/-4.1%) than the saphenous veins (33.4+/-4.1%). At 10(-7) mol/l, DNP resulted in less arterial relaxation compared with atrial and C-type natriuretic peptides and similar relaxation to brain natriuretic peptide. In veins, DNP caused the greatest relaxation of the natriuretic peptides. DNP increased tissue cyclic guanosine monophosphate (cGMP) determined by radioimmunoassay by over 7-fold. Barium chloride and indomethacin attenuated DNP mediated vasorelaxation. However, glibenclamide, charydotoxin, apamin, tetraethyl-ammonium chloride and diisothiocyanato-stilbene-2,2'-disulfonic acid did not. DNP mediated vasorelaxation was mildly attenuated with removal of the endothelium. DNP immunoreactivity was identified in both arteries and veins.


CONCLUSIONS
The current study demonstrates that DNP is an endogenous human natriuretic peptide that relaxes human arteries more than veins. Furthermore, DNP mediated vasorelaxation involves the inward rectifying potassium channels, prostaglandins, and cGMP. This newest member of the natriuretic peptide family may have an important physiologic role in the human vasculature.
Best
Patricia J M
PJ
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Burnett
John C
JC
Wilson
Stephanie H
SH
Holmes
David R
DR
Lerman
Amir
A
D018118:Chloride Channels / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology*; D004730:Endothelium, Vascular / Q000502:physiology; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D008323:Mammary Arteries / Q000187:drug effects* / Q000502:physiology; D045283:Natriuretic Agents / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology; D009924:Organ Culture Techniques; D010455:Peptides / Q000494:pharmacology*; D015221:Potassium Channels / Q000502:physiology; D012501:Saphenous Vein / Q000187:drug effects* / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects*
D018118:Chloride Channels; C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D045283:Natriuretic Agents; D010455:Peptides; D015221:Potassium Channels; D009569:Nitric Oxide; D007213:Indomethacin