Best Patricia J M, Burnett John C, Wilson Stephanie H, Holmes David R, Lerman Amir
Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, 200 First Street SW, Rochester, MN 55905, USA.
Cardiovasc Res. 2002 Aug 1;55(2):375-84. doi: 10.1016/s0008-6363(02)00402-9.
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.
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.
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.
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.
树眼镜蛇利钠肽（DNP）是利钠肽家族的最新成员，是人体内的一种循环肽。DNP对人体血管系统的作用尚不清楚。由于已知其他利钠肽可引起血管舒张，我们在体外测定了人体血管对DNP的反应。我们还研究了DNP介导血管舒张的机制。
将人乳内动脉和大隐静脉环悬挂于器官浴槽中。获得对累积浓度DNP的反应。使用抑制剂来确定这种血管舒张的机制。
DNP引起剂量依赖性舒张，对乳内动脉的作用更大（10⁻⁷mol/L DNP引起的舒张：80.6±4.1%），比对大隐静脉的作用（33.4±4.1%）大。在10⁻⁷mol/L时，与心房利钠肽和C型利钠肽相比，DNP引起的动脉舒张较小，与脑利钠肽引起的舒张相似。在静脉中，DNP引起的利钠肽舒张作用最大。通过放射免疫测定，DNP使组织环磷酸鸟苷（cGMP）增加超过7倍。氯化钡和吲哚美辛减弱了DNP介导的血管舒张。然而，格列本脲、蝎毒素、蜂毒明肽、四乙氯化铵和二异硫氰酸根合芪-2,2'-二磺酸没有这种作用。去除内皮后，DNP介导的血管舒张略有减弱。在动脉和静脉中均鉴定出DNP免疫反应性。
当前研究表明，DNP是一种内源性人体利钠肽，对人体动脉的舒张作用大于静脉。此外，DNP介导的血管舒张涉及内向整流钾通道、前列腺素和cGMP。利钠肽家族的这一最新成员可能在人体血管系统中具有重要的生理作用。
