Vascular tone and angiogenesis modulation by catecholamine coordinated to ruthenium

Abstract

Catecholamines participate in angiogenesis, an important tumor development process. 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. 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 [Ru(NH₃)₄(catecholamine-R)]Cl. 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. [Ru(NH₃)₄(catecholamine-R)]Cl acted as partial agonists and/or antagonists of their respective receptors and induced calcium mobilization. [Ru(NH₃)₄(isoproterenol)]⁺ [Ru(NH₃)₄(noradrenaline)]⁺, and [Ru(NH₃)₄(adrenaline)]⁺ behaved as antiangiogenic complexes, whereas [Ru(NH₃)₄(dopamine)]⁺ proved to be a proangiogenic complex. In conclusion, catecholamines and [Ru(NH₃)₄(catecholamine-R)]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.