TY - JOUR
T1 - Dendroaspis natriuretic peptide relaxes isolated human arteries and veins
AU - Best, Patricia J.M.
AU - Burnett, John C.
AU - Wilson, Stephanie H.
AU - Holmes, David R.
AU - Lerman, Amir
N1 - Funding Information:
National Institutes of Health training grant HL07111-21D, Miami Heart Research Institute, Bruce and Ruth Rappaport Program in Vascular Biology, and the Mayo Foundation supported this work. We would like to thank the technical assistance of Paula Carlson.
PY - 2002
Y1 - 2002
N2 - 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.
AB - 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.
KW - K-channel
KW - Natriuretic peptide
KW - Prostaglandins
KW - Vasoactive agents
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U2 - 10.1016/S0008-6363(02)00402-9
DO - 10.1016/S0008-6363(02)00402-9
M3 - Article
C2 - 12123777
AN - SCOPUS:0036063401
SN - 0008-6363
VL - 55
SP - 375
EP - 384
JO - Cardiovascular research
JF - Cardiovascular research
IS - 2
ER -