Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, SP, Brazil; Department of Health Studies, Metropolitan University of Santos (UNIMES), Santos, SP, Brazil.
Faculty of Medical Sciences, Department of Pharmacology, University of Campinas (UNICAMP), Campinas, SP, Brazil.
Comp Biochem Physiol C Toxicol Pharmacol. 2024 Nov;285:110003. doi: 10.1016/j.cbpc.2024.110003. Epub 2024 Aug 13.
Mammalian and reptilian vascular tissues present basal release of 6-nitrodopamine, which is reduced when the tissues are pre-incubated with the NO synthase inhibitor L-N-Nitro arginine methyl ester (L-NAME), or when the endothelium is mechanically removed. 6-Nitrodopamine induces vasorelaxation in pre-contracted vascular rings by antagonizing the dopaminergic D receptor. Here it was investigated whether male swine vessels (including carotid, left descendent coronary, renal, and femoral arteries) release 6-nitrodopamine, dopamine, noradrenaline, and adrenaline, as measured by liquid chromatography coupled to tandem mass spectrometry. The in vitro vasorelaxant action of 6-nitrodopamine was evaluated in carotid, coronary, renal, and femoral arteries precontracted by U-46619 (3 nM), and compared to that induced by the dopamine D-receptor antagonist L-741,626. Expression of tyrosine hydroxylase and the neuromaker calretinin was investigated by immunohistochemistry. All vascular tissues presented basal release of endothelium-derived catecholamines. The relaxation induced by 6-nitrodopamine was not affected by preincubation of the tissues with either L-NAME (100 μM, 30-min preincubation) or the heme-site inhibitor of soluble guanylyl cyclase ODQ (100 μM, 30-min preincubation). Electrical field stimulation (EFS)-induced contractions were significantly potentiated by previous incubation with L-NAME, but unaffected by ODQ preincubation. The contractions induced by EFS were reduced by preincubation with either 6-nitrodopamine or L-741,626. Immunohistochemistry in all arteries revealed the presence of tyrosine hydroxylase in the endothelium, whereas immunoreactivity for calretinin was negative. Swine vessels present basal release of endothelium-derived catecholamines and expression of tyrosine hydroxylase in the endothelium. The vasodilation induced by 6-nitrodopamine is due to blockade of dopaminergic D-like receptors.
哺乳动物和爬行动物体血管组织基础释放 6-硝基多巴胺,当组织用一氧化氮合酶抑制剂 L-N-硝基精氨酸甲酯(L-NAME)孵育或内皮细胞被机械去除时,其释放减少。6-硝基多巴胺通过拮抗多巴胺 D 受体拮抗作用诱导预收缩血管环的血管舒张。在这里,研究了雄性猪血管(包括颈动脉、左降冠状动脉、肾动脉和股动脉)是否释放 6-硝基多巴胺、多巴胺、去甲肾上腺素和肾上腺素,通过液相色谱-串联质谱法测量。在颈动脉、冠状动脉、肾动脉和股动脉中,通过 U-46619(3 nM)预收缩,评估 6-硝基多巴胺的体外血管舒张作用,并与多巴胺 D 受体拮抗剂 L-741,626 诱导的作用进行比较。通过免疫组织化学研究酪氨酸羟化酶和神经标志物钙视网膜蛋白的表达。所有血管组织均呈现基础分泌内皮衍生儿茶酚胺。6-硝基多巴胺诱导的舒张作用不受组织用 L-NAME(100 μM,30 分钟预孵育)或可溶性鸟苷酸环化酶血红素结合位点抑制剂 ODQ(100 μM,30 分钟预孵育)预孵育的影响。电刺激(EFS)诱导的收缩通过先前用 L-NAME 孵育显著增强,但不受 ODQ 预孵育的影响。EFS 诱导的收缩通过 6-硝基多巴胺或 L-741,626 的预孵育而减少。所有动脉的免疫组织化学显示内皮存在酪氨酸羟化酶,而钙视网膜蛋白的免疫反应性为阴性。猪血管基础分泌内皮衍生儿茶酚胺和内皮表达酪氨酸羟化酶。6-硝基多巴胺诱导的血管舒张是由于多巴胺 D 样受体的阻断。