Vascular tone and angiogenesis modulation by catecholamine coordinated to ruthenium.

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(NH)(catecholamine-R)]Cl.

In the View of Endothelial Microparticles: Novel Perspectives for Diagnostic and Pharmacological Management of Cardiovascular Risk during Diabetes Distress.

Acute or chronic exposure to diabetes-related stressors triggers a specific psychological and behavior stress syndrome called diabetes distress, which underlies depressive symptoms in most diabetic patients. Distressed and/or depressive diabetic adults exhibit higher rates of cardiovascular mortality and morbidity, which have been correlated to macrovascular complications evoked by diabetic behavior stress. Recent experimental findings clearly point out that oxidative stress accounts for the vascular dysfunction initiated by the exposure to life stressors in diabetic conditions.

New Horizons on Molecular Pharmacology Applied to Drug Discovery: When Resonance Overcomes Radioligand Binding.

One of the cornerstones of rational drug development is the measurement of molecular parameters derived from ligand-receptor interaction, which guides therapeutic windows definition. Over the last decades, radioligand binding has provided valuable contributions in this field as key method for such purposes. However, its limitations spurred the development of more exquisite techniques for determining such parameters.

Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored.

MAS-mediated antioxidant effects restore the functionality of angiotensin converting enzyme 2-angiotensin-(1-7)-MAS axis in diabetic rat carotid.

We hypothesized that endothelial AT1-activated NAD(P)H oxidase-driven generation of reactive oxygen species during type I-diabetes impairs carotid ACE2-angiotensin-(1-7)-Mas axis functionality, which accounts for the impaired carotid flow in diabetic rats. We also hypothesized that angiotensin-(1-7) chronic treatment of diabetic rats restores carotid ACE2-angiotensin-(1-7)-Mas axis functionality and carotid flow. Relaxant curves for angiotensin II or angiotensin-(1-7) were obtained in carotid from streptozotocin-induced diabetic rats.

Cross-talk with β2 -adrenoceptors enhances ligand affinity properties from endothelial alpha1 D -adrenoceptors that mediates carotid relaxation.

Objectives: Our main objectives were to investigate the affinity properties of endothelial and muscular α1D -adrenoceptors and to characterize the cross-talk between endothelial α1D -adrenoceptors and β2 -adrenoceptors in rat carotid.

Methods: Relaxation and contraction concentration-response curves for phenylephrine (α1 -adrenergic agonist) were obtained in carotid rings in absence or presence of increasing concentrations of BMY7378 (α1D -adrenergic antagonist), combined or not with increasing concentration of ICI-118,551 (β2 -adrenergic antagonist). Schild analysis was used to estimate the affinity constant from pA2 values of BMY7378.

The role of reactive oxygen species in the modulation of the contraction induced by angiotensin II in carotid artery from diabetic rat.

The modulation played by reactive oxygen species on the angiotensin II-induced contraction in type I-diabetic rat carotid was investigated. Concentration-response curves for angiotensin II were obtained in endothelium-intact or endothelium-denuded carotid from control or streptozotocin-induced diabetic rats, pre-treated with tiron (superoxide scavenger), PEG-catalase (hydrogen peroxide scavenger), dimethylthiourea (hydroxyl scavenger), apocynin [NAD(P)H oxidase inhibitor], SC560 (cyclooxygenase-1 inhibitor), SC236 (cyclooxygenase-2 inhibitor) or Y-27632 (Rho-kinase inhibitor). Reactive oxygen species were measured by flow cytometry in dihydroethidium (DHE)-loaded endothelial cells.