Sakai H, Ikomi F, Ohhashi T
The First Department of Physiology, Shinshu University School of Medicine, Matsumoto 390-8621, Japan.
Am J Physiol. 1999 Aug;277(2):H459-66. doi: 10.1152/ajpheart.1999.277.2.H459.
A mode of action of endothelin (ET) on spontaneous contractions was investigated in ring preparations of isolated bovine mesenteric lymphatics. ET-1 at concentrations between 10(-10) and 10(-9) M caused a dose-dependent increase in the frequency of spontaneous contractions. The specific ET(A)-receptor antagonist BQ-123 (5 x 10(-7) M) caused a significant inhibition of the ET-1-induced positive chronotropic effect in the ring preparations with and without the endothelium. Mechanical denudation of the lymphatic endothelial cells produced a significant potentiation of the ET-induced positive chronotropic effect. BQ-3020 (10(-8)-10(-7) M), a selective ET(B)-receptor agonist, induced dose dependently negative chronotropic and inotropic effects on the spontaneous contractions in the ring preparations with intact endothelium. Mechanical removal of the endothelium caused a significant reduction of the BQ-3020-induced negative chronotropic and inotropic effects. The ET-1-induced positive chronotropic effect was potentiated by pretreatment with N(omega)-nitro-L-arginine methyl ester (L-NAME) (10(-5) M) but unaffected by aspirin (10(-5) M). Additional treatment with L-arginine (10(-4) M) completely reversed the L-NAME-mediated potentiation of the ET-induced chronotropic effect. These results suggest that stimulation of ET(A) receptors on the lymphatic smooth muscles causes a positive chronotropic effect on the spontaneous contractions, and stimulation of ET(B) receptors on the lymphatic endothelial cells induces a release of nitric oxide, which results in the chronotropic and inotropic effects on spontaneous contractions in isolated bovine mesenteric lymphatics.
在内皮素（ET）对自发性收缩的作用方式的研究中，采用了分离的牛肠系膜淋巴管环行标本。浓度在10^(-10)至10^(-9)M之间的ET-1可引起自发性收缩频率呈剂量依赖性增加。特异性ET(A)受体拮抗剂BQ-123（5×10^(-7)M）可显著抑制ET-1在有或无内皮的环行标本中诱导的正性变时效应。淋巴管内皮细胞的机械剥脱可显著增强ET诱导的正性变时效应。选择性ET(B)受体激动剂BQ-3020（10^(-8)-10^(-7)M）对有完整内皮的环行标本中的自发性收缩剂量依赖性地诱导负性变时和变力效应。机械去除内皮可显著降低BQ-3020诱导的负性变时和变力效应。ET-1诱导的正性变时效应可被N(ω)-硝基-L-精氨酸甲酯（L-NAME）（10^(-5)M）预处理增强，但不受阿司匹林（10^(-5)M）影响。额外用L-精氨酸（10^(-4)M）处理可完全逆转L-NAME介导的ET诱导的变时效应增强。这些结果表明，刺激淋巴管平滑肌上的ET(A)受体可对自发性收缩产生正性变时效应，而刺激淋巴管内皮细胞上的ET(B)受体可诱导一氧化氮释放，从而对分离的牛肠系膜淋巴管中的自发性收缩产生变时和变力效应。
