卵巢切除大鼠降钙素基因相关肽、乙酰胆碱和去甲肾上腺素血管效应的变化(英文)  

Alteration of calcitonin gene-related peptide,acetylcholine, and norepinephrine induced vascular responses in ovariectomized rats

作　　者：王望[1] 王宪[1] 

机构地区：[1]北京大学第三医院血管医学研究所,北京100083

出　　处：《中国药理学与毒理学杂志》2003年第5期338-344,共7页Chinese Journal of Pharmacology and Toxicology

基　　金：国家重大基础研究项目 (G2 0 0 0 0 5690 8)~~

摘　　要：目的　研究雌性大鼠卵巢切除和雌激素替代治疗 4个月后 ,血管活性物质对离体动脉作用的改变。方法　采用双侧卵巢切除的雌性大鼠 ,分为假手术组、去卵巢组 (8周龄切除双侧卵巢 )和雌激素替代组 (苯甲雌二醇 40 μg,sc ,每日 1次 ,卵巢切除后 1 4d开始给药至切除后 4个月 )。于给药结束时取升主动脉、胸主动脉及尾动脉 ,进行离体血管功能实验 ,观察对降钙素基因相关肽 (CGRP)、乙酰胆碱(ACh)及去甲肾上腺素 (NE)的反应。结果　卵巢切除 4个月使CGRP引起的大鼠升主动脉舒张最大效应明显降低 ,而对胸主动脉无影响 ;同时ACh对胸主动脉的舒张效应曲线明显右移 ,而对升主动脉无影响。雌激素替代治疗使上述变化反转。去卵巢组的各类动脉对NE的反应性无变化 ,而雌激素替代组的升主动脉和胸主动脉对NE引起的最大收缩效应明显降低。在尾动脉 ,去卵巢组和雌激素替代组的CGRP和NE反应性均无改变。结论　内源性雌激素可以通过多种途径调节血管反应性 ,发挥其心血管保护作用。AIM To determine the role of intrinsic estrogen in the modulation of vascular responses to various agents . METHODS Ov ariectomized rats with or without estrogen (β-estrodiol-3-benzoate 40 μg, s c, once daily, 14 d after bilaterally ovariectomy at 8 weeks age for 4 months) r eplacement were raised for four months. Vascular responses to calcitonin gene-r elated peptide (CGRP), acetylcholine, and norepinephrine were tested on three di fferent arteries (ascending aorta, thoracic aorta, and caudal artery) by functio nal experiments. RESULTS Four months after ovariectomy, the maxim al relaxation induced by CGRP was significantly lowered in ascending aorta but not in thoracic aorta. The EC 50 value for acetylcholine-induced relaxation s hifted to the right in thoracic aorta but not in ascending aorta. Estrogen substitutio n reversed these effects. As for the response to nor- epinephrine, no diffe rence w as found after ovariectomy, but estrogen replacement lowered the maximal respons e to norepinephrine. Ovariectomy did not influence the response to CGRP and nore pinephrine in caudal artery. CONCLUSION Endogenous estrogen has pro tective effects on vasoresponsiveness through different mechanisms. This study g ives further support to the hormone replacement therapy for postmenopausal women .

关 键 词：卵巢切除术 降钙素基因相关肽 乙酰胆碱 去甲肾上腺素 动脉 血管效应 

分 类 号：R458.7[医药卫生—治疗学]