Effects of 17 beta-estradiol on coronary microvascular responses to endothelin-1

Effects of 17 beta-estradiol on coronary microvascular responses to endothelin-1
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DOI:
10.1152/ajpheart.1996.271.3.h1117
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发表时间:
1996-09-01
影响因子:
4.8
通讯作者:
Nuno, DW
Nuno, DW
中科院分区:
医学2区
文献类型:
--
作者:
Lamping, KG;Nuno, DW

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本研究的目的是研究17 β-雌二醇对冠状动脉微血管对内皮素-1(ET-1)反应的影响。使用雄性或雌性犬左心室的离体加压冠状动脉微血管,雄性和雌性犬的血管对ET-1的收缩相似。17 β-雌二醇(1 μ M)类似地减弱雄性(10 μ M对照组收缩百分比:39 +/-9%,雌二醇:3 +/- 2%; P < 0.05)和雌性(10 μ M对照组收缩百分比:39 +/-8%,雌二醇:6 +/- 3%; P < 0.05)狗的小动脉对ET-1的收缩。相反,睾酮(1 μ M)对ET-1的收缩没有影响。选择性ET(A)受体拮抗剂BQ-123(1 μ M)完全消除了对ET-1的收缩,并被选择性ET(B)受体拮抗剂BQ-788(1 μ M)增强。吲哚美辛(Indo,10 μ M)或N-G-硝基-L-精氨酸(L-NNA,100 μ M)不改变ET-1单独引起的收缩。17 β-雌二醇对ET-1预收缩的冠状动脉微血管产生剂量依赖性舒张作用,这与睾酮和孕酮的反应相似。单独使用Indo或L-NNA对17 β-雌二醇的松弛没有影响。然而,Indo和L-NNA的组合减弱了对17 β-雌二醇的舒张(在1 μ M对照下的扩张百分比:64 +/-13%; Indo加L-NNA:21 +/-6%; P < 0.05),但不影响对睾酮的舒张。因此,17 β-雌二醇衰减冠状动脉微血管收缩ET-1比类似浓度的睾酮。17 β-雌二醇调节对内皮素反应的能力可能涉及17 β-雌二醇释放血管扩张剂β-肾上腺素和/或一氧化氮。
The objective of this study was to examine the effects of 17 beta-estradiol on responses of coronary microvessels to endothelin-1 (ET-1). With the use of isolated pressurized coronary microvessels from the left ventricle of male or female dogs, constrictions to ET-1 were similar in vessels from male and female dogs. 17 beta-Estradiol (1 mu M) attenuated constriction to ET-1 of small arteries from both male (percent constriction at 10 mu M control: 39 +/- 9%, estradiol: 3 +/- 2%; P < 0.05) and female (percent constriction at 10 mu M control: 39 +/- 8%, estradiol: 6 +/- 3%; P < 0.05) dogs similarly. In contrast, testosterone (1 mu M) had no effect on constriction to ET-1. Constrictions to ET-1 were completely abolished by BQ-123 (1 mu M), a selective ET(A)-receptor antagonist, and enhanced by BQ-788 (1 mu M), a selective ET(B)-receptor antagonist. Constrictions to ET-1 alone were not altered by indomethacin (Indo, 10 mu M) or N-G-nitro-L-arginine (L-NNA, 100 mu M). 17 beta-Estradiol produced dose-dependent relaxation of coronary microvessels preconstricted with ET-1 that was similar to the response to testosterone and progesterone. Indo or L-NNA alone had no effect on relaxation to 17 beta-estradiol. However, the combination of Indo and L-NNA attenuated relaxation to 17 beta-estradiol (percent dilation at 1 mu M control: 64 +/- 13%; Indo plus L-NNA: 21 +/- 6%; P < 0.05) but did not affect relaxation to testosterone. Thus 17 beta-estradiol attenuated constrictions of coronary microvessels to ET-1 more than did similar concentrations of testosterone. The ability of 17 beta-estradiol to modulate responses to endothelin may involve release of vasodilator prostaglandins and/or nitric oxide by 17 beta-estradiol.