Deakin University, School of Life and Environmental Sciences, Waurn Ponds Campus, Geelong, Victoria, Australia.
Discipline of Physiology, School of Medical Sciences, The University of Sydney, Sydney, New South Wales, Australia.
Am J Physiol Regul Integr Comp Physiol. 2019 Sep 1;317(3):R379-R385. doi: 10.1152/ajpregu.00319.2018. Epub 2019 Jun 26.
In this study, myography was used to determine the effect of arterial size on nitric oxide (NO) vasodilatory mechanisms in the hindlimb vasculature of the toad . Immunohistochemical analysis showed NO synthase (NOS) 1 immunoreactivity in perivascular nitrergic nerves in the iliac and sciatic arteries. Furthermore, NOS3 immunoreactivity was observed in the vascular smooth muscle of the sciatic artery, but not the endothelium. Acetylcholine (ACh) was used to facilitate intracellular Ca signaling to activate vasodilatory pathways in the arteries. In the iliac artery, ACh-mediated vasodilation was abolished by blockade of the soluble guanylate cyclase pathway with the soluble guanylate cyclase inhibitor ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, 10 M) and blockade of the prostaglandin signaling pathway with indomethacin (10 M). Furthermore, disruption of the endothelium had no effect on the ACh-mediated vasodilation in the iliac artery, and generic inhibition of NOS with -nitro-l-arginine (3 × 10 M) significantly inhibited the vasodilation, indicating NO signaling. In contrast to the iliac artery, ACh-mediated vasodilation of the sciatic artery had a significant endothelium-dependent component. Interestingly, the vasodilation was not significantly affected by -nitro-l-arginine, but it was significantly inhibited by the specific NOS1 inhibitor -(1-imino-3-butenyl)-l-ornithine (vinyl-l-NIO, 10 M). ODQ mostly inhibited the ACh-mediated vasodilation. In addition, indomethacin also significantly inhibited the ACh-mediated vasodilation, indicating a role for prostaglandins in the sciatic artery. This study found that the mechanisms of vasodilation in the hindlimb vasculature of vary with vessel size and that the endothelium is involved in vasodilation in the smaller sciatic artery.
在这项研究中，肌动电流描记术被用于确定动脉大小对蟾蜍后肢血管一氧化氮（NO）血管舒张机制的影响。免疫组织化学分析显示，髂动脉和坐骨动脉的血管周围氮能神经中存在一氧化氮合酶（NOS）1 免疫反应性。此外，在坐骨动脉的血管平滑肌中观察到 NOS3 免疫反应性，但在内皮细胞中没有观察到。乙酰胆碱（ACh）被用于促进细胞内 Ca 信号转导，以激活动脉中的血管舒张途径。在髂动脉中，ACh 介导的血管舒张被可溶性鸟苷酸环化酶抑制剂 ODQ（1H-[1,2,4]恶二唑并[4,3-a]喹喔啉-1-酮，10 μM）阻断可溶性鸟苷酸环化酶途径和吲哚美辛（10 μM）阻断前列腺素信号通路所消除。此外，破坏内皮细胞对髂动脉中 ACh 介导的血管舒张没有影响，而使用 L-硝基精氨酸（3×10 μM）对 NOS 的一般抑制显著抑制了血管舒张，表明存在 NO 信号。与髂动脉相反，坐骨动脉中 ACh 介导的血管舒张具有显著的内皮依赖性成分。有趣的是，L-硝基精氨酸对血管舒张没有显著影响，但特异性 NOS1 抑制剂 -（1-亚氨基-3-丁烯基）-L-鸟氨酸（乙烯基-L-NIO，10 μM）显著抑制了血管舒张。ODQ 主要抑制 ACh 介导的血管舒张。此外，吲哚美辛也显著抑制了 ACh 介导的血管舒张，表明前列腺素在坐骨动脉中起作用。本研究发现，后肢血管舒张的机制因血管大小而异，并且内皮细胞参与了较小的坐骨动脉的血管舒张。
