内皮的存在掩盖了邻苯三酚与亚甲蓝直接舒张大鼠肠系膜动脉的效应(英文)

Presence of endothelium masks direct vasodilator effects of pyrogallol and methylthioninium chloride in perfused rat mesenteric artery

在灌注的大鼠肠系膜血管,邻苯三酚与亚甲蓝能增强甲氧胺或电刺激释放去甲肾上腺素的缩血管效应。然而,当亚硝基精氨酸甲酯存在或去内皮时,两者可抑制TNS所致的缩血管效应,去除内皮后,邻苯三酚与亚甲蓝产生浓度依赖性舒血管效应,结果提示,血管内皮存在可能掩盖邻苯三酚与亚甲蓝两者的直接舒张血管平滑肌作用。

In the perfused rat mesenteric artery vasoconstrictor responses to transmural nerve stimulation (TNS) were enhanced by pyrogallol (Pyr) 0.1 mmol·L-1 or methylthioninium chloride (Met) 0.01 mmol·L-1. But the duration of the effect of Pyr was brief, while the effect of Met remained stable. Met, but not Pyr, slightly increased the basal level of perfu-sion pressure. Contractile responses to the alpha adrenergic agonist methoxamine were also potentiated by both Pyr and Met, and in both cases their effects persisted as long as Pyr or Met was present. Super-oxide dismutase (SOD) abolished or inhibited the po-tentiation produced by Pyr or Met. Both Pyr and Met inhibited the vasodilation produced by acetylcholine (ACh). However, after blockade of endothelial function both Pyr and Met inhibited vasoconstrictor re-'ponses to TNS in the presence of N-nitro-L-arginine lethyl ester (L-NAME) 0.1 mmol·L-1, an inhibitor of nitric oxide synthesis, or removal of endothelium. After removal of endothelium both Pyr and Met produced vasodilator responses in a concentration-depen- dent manner. These results suggest that the ability of both Pyr and Met to potentiate contractile responses and inhibit vasodilator responses to ACh is due to generation of superoxide anion, and that the actions of Met may also involve direct inactivation of guanylate cyclase. The present study also suggests that both Pyr and Met have direct relaxing effects on vascular smooth muscle, effects which are masked by enhancing actions in the presence of endothelium.