Momoi Hiroki, Ikomi Fumitaka, Ohhashi Toshio
The 1st Department of Physiology, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621 Japan.
Jpn J Physiol. 2003 Jun;53(3):193-203. doi: 10.2170/jjphysiol.53.193.
We examined chronic effects of 17beta-estradiol (E(2)beta) on the responses of isolated rat anterior cerebral small arteries to vasoactive substances with special reference to endothelial function. Female Sprague-Dawley rats were separated into four groups: (1) sham-operated group (Sham), (2) sham-operated plus E(2)beta treated group (Sham+E), (3) ovariectomized group (OVX), (4) ovariectomized plus E(2)beta treated group (OVX+E). 5-Hydroxytryptamine (5-HT) (10(-10)-10(-3) M) and U46619 (10(-15)-10(-8) M) induced concentration-dependent contractions in the cerebral small arteries. The 5-HT- and U46619-induced contractions were not affected by pretreatment with 3 x 10(-5) M N(omega)-nitro-L-arginine methyl ester (L-NAME). No significant difference in high potassium (80 mM)- and the agonists-mediated contractions was observed among the four groups. Administration of acetylcholine (ACh) (10(-9)-10(-3) M) and sodium nitroprusside (SNP) (10(-8)-10(-3) M) caused dose-related relaxations in the cerebral small arteries precontracted by 10(-8) M U46619. Chronic treatment with E(2)beta caused a significant potentiation of the ACh-induced relaxations in the Sham+E and OVX+E groups. The dose-response curve for ACh in the OVX group was quite similar to that obtained with the Sham group. The ACh-induced relaxation was reduced significantly by pretreatment with 3 x 10(-5) M L-NAME, and an additional treatment with 10(-3) M L-arginine reversed significantly the L-NAME-induced inhibition. The removal of endothelial cells produced a significant reduction of the ACh-induced relaxation. Indomethacin (10(-5) M) did not alter the ACh-induced relaxation. The findings suggest that E(2)beta potentiates ACh-induced endothelium-dependent relaxation in rat anterior cerebral arteries and that the potentiation may be, in part, mediated by increasing production and release of endogenous NO from the endothelial cells.
我们研究了17β-雌二醇（E₂β）对离体大鼠大脑前小动脉对血管活性物质反应的慢性影响，并特别关注内皮功能。将雌性Sprague-Dawley大鼠分为四组：（1）假手术组（Sham），（2）假手术加E₂β处理组（Sham+E），（3）卵巢切除组（OVX），（4）卵巢切除加E₂β处理组（OVX+E）。5-羟色胺（5-HT）（10⁻¹⁰ - 10⁻³ M）和U46619（10⁻¹⁵ - 10⁻⁸ M）在大脑小动脉中诱导浓度依赖性收缩。5-HT和U46619诱导的收缩不受3×10⁻⁵ M N⁻硝基-L-精氨酸甲酯（L-NAME）预处理的影响。四组之间在高钾（80 mM）和激动剂介导的收缩方面未观察到显著差异。给予乙酰胆碱（ACh）（10⁻⁹ - 10⁻³ M）和硝普钠（SNP）（10⁻⁸ - 10⁻³ M）可使由10⁻⁸ M U46619预收缩的大脑小动脉产生剂量相关的舒张。E₂β的慢性处理导致Sham+E组和OVX+E组中ACh诱导的舒张显著增强。OVX组中ACh的剂量反应曲线与Sham组获得的曲线非常相似。ACh诱导的舒张通过3×10⁻⁵ M L-NAME预处理显著降低，并且用10⁻³ M L-精氨酸的额外处理显著逆转了L-NAME诱导的抑制。去除内皮细胞导致ACh诱导的舒张显著降低。吲哚美辛（10⁻⁵ M）未改变ACh诱导的舒张。这些发现表明，E₂β增强了大鼠大脑前动脉中ACh诱导的内皮依赖性舒张，并且这种增强可能部分是由内皮细胞内源性NO的产生和释放增加介导的。
