Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.
Potentiation of norepinephrine-induced contractions by endothelin-1 in the rabbit aorta.
复制标题
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
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Laher,I
中科院分区：
文献类型：
--
作者：
Henrion,D;Laher,I
亚阈值浓度的内皮素-1增强去甲肾上腺素诱导的兔主动脉等长环收缩。内皮素-1(0.1 nM)预处理10分钟可增加主动脉环对去甲肾上腺素的敏感性，但不影响最大收缩。这种扩增不受内皮细胞去除的影响，但可被蛋白激酶C抑制剂星形孢子素(0.01微米)和钙磷蛋白C(0.1微米)阻止。用佛波醇12-肉豆蔻酸酯-13-醋酸酯(0.1微米)对主动脉环进行24小时的预处理也可消除这种增强作用。用佛波酯(10 NM)处理去甲肾上腺素引起的收缩，并将K+浓度从4.6 mM增加到8.6 mM，可增强去甲肾上腺素引起的收缩。内皮素-1(0.1 nM)或佛波酯(10 NM)对去甲肾上腺素引起的收缩的增强作用与去甲肾上腺素引起的~(45)Ca~(2+)摄取或内流增加无关，而K~+浓度从4.6 mM增加到8.6 mM则与去甲肾上腺素引起的~(45)Ca~(2+)摄取增加有关。我们得出结论，内皮素-1对去甲肾上腺素引起的收缩的增强作用发生在刺激的Ca~(2+)内流没有变化的情况下，并且不依赖于内皮。内皮素-1可能通过激活蛋白激酶C依赖的机制来增加收缩装置对钙离子的敏感性。
Subthreshold concentrations of endothelin-1 potentiated the norepinephrine-induced contraction in isometrically mounted rings of the rabbit aorta. Pretreatment with endothelin-1 (0.1 nM) for 10 minutes increased the sensitivity of the aortic rings to norepinephrine without affecting the maximal contraction. This amplification was unaffected by removal of the endothelium but was prevented by the protein kinase C inhibitors staurosporine (0.01 microM) and calphostin C (0.1 microM). Pretreatment of the aortic rings for 24 hours with phorbol 12-myristate 13-acetate (0.1 microM) also abolished the potentiation. Norepinephrine-induced contraction was potentiated by pretreating with phorbol 12-myristate 13-acetate (10 nM) and by increasing the concentration of K+ in the bath solution from 4.6 to 8.6 mM. The potentiation of the norepinephrine-induced contraction by endothelin-1 (0.1 nM) or by phorbol 12-myristate 13-acetate (10 nM) was not associated with an increase in norepinephrine-induced 45Ca2+ uptake or influx, whereas the potentiation due to an increase in the concentration of K+ in the bath solution from 4.6 to 8.6 mM was associated with an increase in norepinephrine-induced 45Ca2+ uptake. We conclude that endothelin-1 potentiation of the norepinephrine-induced contraction occurs in the absence of changes in stimulated Ca2+ entry and is endothelium independent. It is probable that endothelin-1 increases the sensitivity of the contractile apparatus to Ca2+ by activating protein kinase C-dependent mechanisms.