生理学报Acta Physiologica Sinica, April

研究论文

血管钠肽对离体人乳内动脉的舒张作用

于军1, 朱妙章1, *, 韦耿泽1, 陈宝莹2, 吕顺艳1, 康云帆3, 郭海涛1, 马恒1,董明清4

1第四军医大学生理学教研室, 2唐都医院放射科, 3西京医院心血管外科中心, 4病理生理学教研室, 西安 710032

摘要: 为了研究血管钠肽(VNP)对人乳内动脉(human intramammary artery, HIMA)的舒张作用及其机制, 采用离体血管灌流的方法, 观察VNP对内皮完整和去内皮HIMA的舒张作用, 以及HS-142-1、TEA、8-Br-cGMP和镁蓝(MB)对这一过程的影响。实验中观察到, VNP (0.0001-1 μmol/L)可引起剂量依赖性的舒张效应, 且无内皮依赖性; 8-Br-cGMP (0.1-1000 μmol/L)也可引起剂量依赖性的血管舒张效应。钠尿肽鸟苷酸环化酶(guanylate cyclase, GC)受体的特异性阻断剂HS-142-1 (20 μmol/L)使VNP舒张HIMA的作用几乎完全消失。MB是GC的抑制剂, 10 μmol/L的MB不但使VNP舒张HIMA的作用完全消失, 而且可增强HIMA对去甲肾上腺素(NE)产生的收缩反应。钙激活钾通道(KCa)的阻断剂 TEA(1mmol/L)可减弱(但是不完全阻断)VNP的舒血管作用。上述结果表明, VNP对HIMA具有不依赖内皮的舒张作用; 此作用是通过作用于平滑肌细胞的钠尿肽GC受体, 引起细胞内的cGMP水平升高实现的, 并且与KCa有关。

关键词: 血管钠肽 ; 人乳内动脉; cGMP; TEA; 镁蓝

中图分类号: Q463; R33

Vasorelaxing role of vasonatrin peptide in human intramammary artery in vitro

YU Jun1, ZHU Miao-Zhang1,*, WEI Geng-Ze1, CHEN Bao-Ying2, LU Shun-Yan1, Kang Yun-Fan3,GUO Hai-Tao1, Ma Heng1, DONG Ming-Qing4

1Department of Physiology, 2Radiology Department of Tangdu Hospital, 3 Cardiovascular Surgery Center of Xijing Hospital, and 4Department of Pathophysiology, Fourth Military Medical University, Xi'an 710032

Abstract: The purpose of this study was to investigate the vasorelaxing effect of vasonatrin peptide (VNP) on human intramammary artery (HIMA).The vasorelaxing effect of VNP on HIMA was measured by means of perfusion in vitro. The effects of HS-142-1, TEA, 8-Br-cGMP and methylene blue (MB) were also observed. It was found that VNP caused a concentration-dependent relaxation in HIMA which was independent of the endothelium. 8-Br-cGMP (0.1-1000 μmol/L) also caused a concentration-dependent relaxation in HIMA. The vasorelaxing effect of VNP disappeared in the presence of HS-142-1 (20 μmol/L), an antagonist of the natriuretic peptide guanylate cyclase (GC) receptor. MB (10 μmol/L), an inhibitor of GC, not only blocked completely the relaxation of HIMA, but also enhanced the vascular contraction induced by norepinephrine. TEA (1mmol/L), an antagonist of calcium activated potassium channels (KCa), reduced but not completely blocked the vasorelaxing effect of VNP. These findings suggest that VNP can relax HIMA, which is independent of the endothelium. This effect is possibly achieved by the binding of VNP with the natriuretic peptide GC receptors in the smooth muscle cells (SMCs), leading to an increase in intracellular cGMP level. Moreover, the vasorelaxing effect of VNP is associated with KCa.

Key words: vasonatrin peptide; human intramammary artery; cGMP; TEA; methylene blue