Amplification effect and mechanism of action of ET-1 in U-46619-induced vasoconstriction in pig skin.
Amplification effect and mechanism of action of ET-1 in U-46619-induced vasoconstriction in pig skin.
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ET-1在U-46619诱导的猪皮血管收缩中的放大作用及作用机制。
DOI：
10.1152/ajpregu.2001.280.3.r713
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发表时间：
2001
期刊：
影响因子：
--
通讯作者：
P. Neligan
中科院分区：
文献类型：
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作者：
C. Pang;H. Xu;N. Huang;C. Forrest;T. Perreault;P. Neligan
本研究的目的是探讨低浓度的内皮素-1 (ET-1; 8 x 10(-10) M) 是否可以在皮肤血管痉挛的发病机制中放大其他血管活性物质的皮肤血管收缩作用。猪皮瓣 (6 x 16 cm) 用在 37 摄氏度和 pH 7.4 下用 95% O(2) 和 5% CO(2) 平衡的 Krebs 缓冲液灌注。通过压力传感器测量的皮肤灌注压力和通过皮肤荧光测定技术评估的皮肤灌注用于评估皮肤血管收缩。我们观察到ET-1 (8 x 10(-10) M)显着放大了去甲肾上腺素的浓度依赖性(10(-7)-10(-5) M)皮肤血管收缩作用。更重要的是，我们首次观察到这种低浓度的ET-1还放大了血栓素A(2)模拟物U-46619的浓度依赖性(10(-8)-10(-6) M)皮肤血管收缩作用，并且ET-1的这种放大作用被蛋白激酶C(PKC)抑制剂白屈菜红碱(5 x 10(-6) M)完全阻断。相反，PKC 激活剂佛波醇 12,13-二丁酸酯 (10(-7) M) 放大了 U-46619 的血管收缩作用。此外，在U-46619诱导的皮肤血管收缩中，皮肤血管系统对细胞外Ca(2+)血管收缩作用的敏感性在8 x 10(-10) M ET-1存在下显着增强。最后，环加氧酶抑制剂吲哚美辛(5 x 10(-6) M)不影响ET-1对U-46619诱导的皮肤血管收缩的放大作用。我们得出结论，低浓度的ET-1可以增强U-46619的皮肤血管收缩作用，不依赖于内源性环氧合酶产物，其机制可能涉及PKC的激活和平滑肌细胞中收缩装置对Ca(2+)的敏感性增加。
The aim of this study was to investigate if a low concentration of endothelin-1 (ET-1; 8 x 10(-10) M) may amplify the skin vasoconstrictor effect of other vasoactive substances in the pathogenesis of skin vasospasm. Pig skin flaps (6 x 16 cm) were perfused with Krebs buffer equilibrated with 95% O(2) and 5% CO(2) at 37 degrees C and pH 7.4. Skin perfusion pressure measured by a pressure transducer and skin perfusion assessed by the dermofluorometry technique were used for assessment of skin vasoconstriction. We observed that ET-1 (8 x 10(-10) M) significantly amplified the concentration-dependent (10(-7)-10(-5) M) skin vasoconstrictor effect of norepinephrine. More importantly, we observed for the first time that this low concentration of ET-1 also amplified the concentration-dependent (10(-8)-10(-6) M) skin vasoconstrictor effect of the thromboxane A(2) mimetic U-46619, and this amplification effect of ET-1 was completely blocked by the protein kinase C (PKC) inhibitor chelerythrine (5 x 10(-6) M). Conversely, the PKC activator phorbol 12,13-dibutyrate (10(-7) M) amplified the vasoconstrictor effect of U-46619. Furthermore, the sensitivity of the skin vasculature to the vasoconstrictor effect of extracellular Ca(2+) in U-46619-induced skin vasoconstriction was significantly enhanced in the presence of 8 x 10(-10) M ET-1. Finally, the cyclooxygenase inhibitor indomethacin (5 x 10(-6) M) did not affect the amplification effect of ET-1 on U-46619-induced skin vasoconstriction. We conclude that a low concentration of ET-1 can amplify the skin vasoconstrictor effect of U-46619 independent of endogenous cyclooxygenase products, and the mechanism may involve activation of PKC and increase in sensitivity of the contractile apparatus to Ca(2+) in smooth muscle cells.
兔主动脉中内皮素-1 增强去甲肾上腺素诱导的收缩。
DOI：
10.1161/01.hyp.22.1.78
发表时间：
1993
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
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作者：
Henrion,D;Laher,I
通讯作者：
Laher,I