![]() The thoracic aorta was quickly removed, cleaned of adherent tissues, cut into rings (4 mm length), placed between two stainless-steel stirrups, and connected to an isometric force transducer (Letica Scientific Instruments, Barcelona, Spain) to measure tension in the vessels. Male Wistar rats (200 g) were killed by decapitation under anesthesia (inhaled isoflurane) the thoracic aorta was used to measure the isometric tension. Animals (Scientific Procedures) Act 1986. 1), where catecholamine is isoproterenol (Iso), dopamine (Dop), noradrenaline (Nor), catechol (Cat), or adrenaline (Adre), and evaluated how these complexes impact vascular tone modulation, calcium mobilization, and angiogenesis induced by the ruthenium-coordinated catecholamine species as compared to the corresponding free-metal catecholamines.Īll the procedures were performed according to the standards and policies of the Ethics Committee on Animal Care and Use of the University of São Paulo (#.60.0), and in accordance with the ARRIVE guidelines U.K. 23– 26 On the basis of a previously published work, 27 here we have synthesized + complexes ( Fig. 22 The dioxolene ligand could exert a chelating effect on some metal ions such as ruthenium. Besides that, ruthenium compounds may be more stable in biological systems due extension of d-orbital, which are found to contribute very strongly to the binding energy and consequently contributing to the thermodynamic stability. Generally, ruthenium species exhibit low toxicity probably due those species display some of the same chemical properties of iron compounds, the most abundant metal center species in human body. Among them ruthenium compounds have been detached due the possibility to synthesize species with biological molecule recognition and interaction. Several metal complexes with different metal ions and ligands of diverse structures have been prepared and studied for their biological activity. Designing an appropriate catecholamine compound to isolate one of the receptor binding sites could provide valuable information about the angiogenesis mechanism. 13, 17– 20 Despite similarities in their chemical structures, these catecholamines present different α- and β-agonist-induced receptor activation profiles: 13, 20, 21 the dioxolene ring and the amine tail might influence the catecholamine interaction with the receptor during the binding process. The most notable catecholamines are dopamine, norepinephrine, and epinephrine, which are endogenous compounds derived from tyrosine. 1, 2 Catecholamines comprise amines bearing a 3,4-dihydroxy-substituted phenyl ring. 1, 2, 11– 16 Therefore, understanding how catecholamines contribute to angiogenesis has become an interesting investigation field. One of the most studied processes regarding angiogenesis has been a catecholamine-induced regulation process. It is regulated by several pro- and antiangiogenic factors, 3, 4, 7– 10 and learning how to control this process has proven to be a great therapeutic strategy. 3– 6 Angiogenesis is a very complex process during which new blood vessels originate from pre-existing vessels. ![]() ![]() In conclusion, catecholamines and Cl can modulate angiogenesis, and catechol group availability can modify the way these complexes impact the vascular tone, suggesting that catecholamines and their receptors interact differently after catecholamine coordination to ruthenium.Ĭancer treatment strategies, including therapy based on the antiangiogenic approach, 1, 2 have been the object of intensive studies. + +, and + behaved as antiangiogenic complexes, whereas + proved to be a proangiogenic complex. Cl acted as partial agonists and/or antagonists of their respective receptors and induced calcium mobilization. We then assessed the angiogenic activity of the complexes in a chorioallantoic membrane model (CAM) and examined vascular reactivity and calcium mobilization in rat aortas and vascular cells. ![]() To evaluate how catechol and amine groups contribute to angiogenesis, we immobilized the catechol site through ruthenium ion (Ru) coordination, to obtain species with the general formula Cl. However, the way catecholamines interact with their receptors has not been completely elucidated, and doubts still remain as to whether these interactions occur between catechol and/or amine sites and particular amino acid residues on the catecholamine receptors. Catecholamines participate in angiogenesis, an important tumor development process. ![]()
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